Tykerb Evaluation After Chemotherapy (TEACH): Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer

A Randomized, Double-blind, Multicenter, Placebo-controlled Study of Adjuvant Lapatinib (GW572016) in Women With Early-Stage ErbB2 Overexpressing Breast Cancer

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00374322

Enrollment

3166

Registered

2006-09-11

Start date

2006-08-31

Completion date

2013-07-31

Last updated

2014-08-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neoplasms, Breast

Keywords

Breast Cancer, ErbB2-overexpressing, early-stage breast cancer, adjuvant

Brief summary

This study was designed to evaluate and compare the safety and efficacy of an oral dual tyrosine kinase inhibitor, lapatinib, versus placebo in women with early-stage ErbB2-overexpressing breast cancer who have completed their primary neoadjuvant or adjuvant chemotherapy and have no clinical or radiographic evidence of disease.

Interventions

DRUGlapatinib

Lapatinib 1500 mg (6 tablets) daily for 12 months

OTHERplacebo

6 tablets daily for 12 months

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Have histologically or cytologically confirmed ErbB2-overexpressing invasive carcinoma (TX or T1-4) of the breast at the time of the initial diagnosis and have undergone adequate excision of tumor; * Had tumors that overexpress ErbB2 defined as 3+ by IHC or c-erbB2 gene amplification by FISH (ErbB2 expression/amplification must be documented prior to study entry; however, a tumor tissue sample must be sent to a central laboratory for subsequent re-analysis of ErbB2 status); * Have Stage I through Stage IIIc disease according to the American Joint Committee on Cancer (6th edition) staging criteria for breast cancer and meet one of the following criteria: node-positive disease defined as: one positive lymph node by sentinel node biopsy OR at least 1 positive lymph node found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN1 or cN2 (if sentinel node biopsy is positive, subject may either undergo an axillary node dissection or radiotherapy to the axilla). node-positive disease evaluated as: ipsilateral axillary lymph nodes cN0-2 by clinical evaluation and axillary lymph nodes pNX, pN0(i+), or pN1-3 by pathological evaluation \[patients with pN3 (Stage IIIc disease) must be disease free following completion of neoadjuvant or adjuvant chemotherapy for at least 12 months and must not have been lost to follow up\]. OR node-negative disease defined as: negative sentinel node biopsy OR no positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN0. node-negative disease categorized as: high-risk disease (tumor \>2.0 cm if ER and/or progesterone receptor (PgR) positive disease is present or tumor \>1.0 cm if ER and PgR negative disease) OR intermediate-risk disease (tumor 1.0-2.0 cm and ER and/or PgR positive disease). * Women with synchronous bilateral invasive breast cancer or synchronous DCIS of either the contralateral or ipsilateral breast at the time of the initial diagnosis are also eligible; * Have undergone either mastectomy OR lumpectomy; * Have received and completed treatment with a neoadjuvant or adjuvant chemotherapy regimen containing either an anthracycline or a taxane; or any cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen; * May continue to receive endocrine therapy while taking study medication, if endocrine therapy was initiated as either adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer or for ovarian function suppression; however, endocrine therapy may not be initiated while taking study medication. Endocrine therapy agents may be switched while participating in this study (e.g., stop tamoxifen and start letrozole); * May have received prior radiotherapy as treatment for primary tumor; however, is not required for study entry; * May continue to receive radiotherapy while taking study medication, if radiotherapy was initiated as adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer; * May continue to receive bisphosphonates only for treatment of documented osteoporosis, but not as treatment or prophylaxis of bone metastases; * All women eligible for adjuvant treatment with trastuzumab, including those diagnosed and treated within the last six months, must be considered for such treatment prior to being offered participation in this study. Participation in this study will be allowed only if the physician and patient have considered and discussed at length the advantages of trastuzumab, but have mutually decided against initiating trastuzumab therapy. * Have clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry; * if signs or symptoms suggestive of either recurrence of disease or metastatic disease are present, the appropriate radiological imaging must be performed * if the following laboratory results are present, the appropriate radiological imaging must be performed: * for AST/ALT ≥2×ULN or ALP ≥2×ULN (not in the bone fraction), an abdominal CT or MRI must be done * for ALP≥2×ULN in the bone fraction, a bone scan must be done; a confirmatory x-ray, CT scan or MRI scan or biopsy is required if the results of the bone scan are inconclusive * Have a unilateral/bilateral mammogram within 12 months prior to study entry; * Have an analysis of both ER and PgR on the primary tumor prior to study entry; * Have a cardiac ejection fraction within institutional range of normal as measured by either echocardiogram or multigated acquisition scans; * Have an Eastern Cooperative Oncology Group Performance Status of 0 to 1; * Women with a history of non-breast malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence. Women with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical carcinoma in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin; * Are able to swallow and retain oral medication; * Have a paraffin-embedded tissue block from an archived tumor tissue from the primary tumor or twenty (20) slides of paraffin-embedded tissue available for biomarker analysis; * Have adequate organ function defined as: absolute neutrophil count ≥1.5× 10\^9/L; hemoglobin ≥9 g/dL; platelets ≥75 × 10\^9/L; albumin ≥2.5 g/dL; serum bilirubin ≤1.25 ×ULN; aspartate aminotransferase and alanine aminotransferase ≤3 × ULN and serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥40 mL/min * Have signed the informed consent form (ICF); * Women of child-bearing potential must have a negative serum pregnancy test at screening and agree to complete abstinence from intercourse or consistent and correct use of an acceptable methods of birth control from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication:

Exclusion criteria

* Have clinical and radiologic evidence of local or regional recurrence of disease or metastatic disease at the time of study entry; * Had metachronous invasive breast cancer (breast cancers diagnosed at different times); * Have a prior history of other breast cancer malignancies, including DCIS; * Are unable to provide archived tumor tissue samples for assay; * Had prior therapy with an ErbB1 and/or ErbB2 inhibitor; women who experienced a hypersensitivity or allergic reaction to trastuzumab during the first infusion and were unable to complete this infusion are eligible; * Receive concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication; * Have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment; * Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded; * Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety; * Have an active or uncontrolled infection; * Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent; * Have a known history of uncontrolled or symptomatic angina, arrhythmias, or CHF; * Are pregnant or breastfeeding; * Receive concurrent treatment with an investigational agent; women, who are in follow-up in another clinical trial where the primary endpoint has been met and the interval between assessments is ≥12 months and radiological imaging is not required at these assessments, are eligible; * Receive concurrent treatment with a selected list of strong inducers and inhibitors of CYP3A4; * Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication; * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients;

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	From randomization until date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause (assessed up to 6 years; 1 year of treatment, 5 years of follow-up [median of 5.3 years for final analysis])	DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ; other second primary cancer (excluding squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast); death from any cause without a prior event. Par. who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Par. who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.

Secondary

Measure	Time frame	Description
Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	From the date of randomization until the date of the first occurrence of an objective disease recurrence or contralateral breast cancer (assessed up to 6 years; 1 year of treatment and 5.3 years of follow-up [median of 5 years for final analysis])	Recurrence is defined as experiencing a recurrence of initial disease or contralateral breast cancer after randomization. Time to first recurrence is defined as the interval between the date of randomization and the date of the first occurrence of an objective disease recurrence or contralateral breast cancer. Time to first recurrence included the first occurrence at one of the following sites as an event: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ (DCIS).
Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	From the date of randomization until the date of the first occurrence of a distant recurrence (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])	Distant recurrence (metastatic disease) is defined as a tumor in any area of the body not including those defined as local or regional recurrence. Sites of distant recurrence include: skin, subcutaneous tissue, and lymph nodes (excluding those described for local and regional recurrence); bone marrow; skeletal; lungs and pleural; ascites and pleural effusions; liver and other viscera; and central nervous system (CNS). Time to distant recurrence is defined as the interval between the date of randomization and the date of the first occurrence of a distant recurrence.
Time to Central Nervous System (CNS) Recurrence	From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])	Time to CNS recurrence is defined as the interval between the date of randomization and the date of the occurrence of a CNS recurrence if noted as part of the participant's first recurrence. Time to CNS recurrence was not calculated; data are presented as the number of participants with CNS recurrence in the subsequent outcome measure table.
Number of Participants With CNS Recurrence	From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])	The number of participants experiencing a CNS recurrence was summarized.
Modified Disease-free Survival (MDFS)	From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)	Modified disease recurrence=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause. The date of the event=the earliest date of the occurrence of any of the following events: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including DCIS; death from any cause without a prior event. MDFS was not calculated; data are presented as the number of participants with any recurrence of the initial disease, contralateral breast cancer, or death (disease-free survival) in the subsequent outcome measure table.
Number of Participants With Any Recurrence of the Initial Disease, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)	DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence and contralateral breast cancer, including ductal carcinoma in situ; or death from any cause without a prior event. Participants who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Participants who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.
Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)	The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The PCS score is a summary score representing overall physical health, which is derived from the 8 domain scores. As with each domain score, the PCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the last observation carried forward (LOCF) method. The scores were analyzed using an analysis of covariance (ANCOVA) model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.
Number of Participants Who Died (Overall Survival)	From the date of randomization until death from any cause (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])	Overall Survival (OS) is defined as the time from randomization until death from any cause. Data are presented as the number of participants who died. For participants who did not die, time to death was censored at the last date the participant was known to be alive.
Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)	The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH) perceptions, vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). Each domain is scored from 0 (poorer health) to 100 (better health); higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.
Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	At Baseline and every 3 months thereafter up to Month 12/Early Withdrawal Visit	The hematology parameters assessed were: basophils (Bs) in giga (10\^9) per liter (GI/L) and in percentage (%), eosinophils (Eo) in GI/L and %, hematocrit, hemoglobin, lymphocytes (Lmph) in GI/L and %, monocytes (Mono) in GI/L and %, platelet count, Red Blood Cell (RBC) count, total neutrophil count (TNC) in GI/L and %, and White Blood Cell (WBC) count. The Baseline (BL) value is the last available pre-treatment result recorded. Any post-Baseline value was based on results recorded at any scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) is presented for BL and any post-Baseline (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.
Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	At Baseline and every 6 weeks thereafter up to Month 12/Early Withdrawal Visit	The clinical chemistry parameters assessed were: alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), bicarbonate, blood urea nitrogen (BUN), bone alkaline phosphatase (Bone ALP), calcium, chloride, creatinine, creatinine clearance (Cr. Clearance), creatinine clearance estimated (Cr. Clrnc. est.), glucose, potassium, sodium, total bilirubin (Total Bln), total protein, urea, and uric acid. The Baseline (BL) value is the last available pre-treatment result recorded. Any post-Baseline value was based on results recorded at scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) was presented for BL and any post-Baseline (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm.
Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	From the first dose of study treatment up to 12 months	Non-laboratory toxicities are defined as adverse events (AEs). The number of partcipants with any treatment-emergent AE of the indicated toxicity grade are summarized. Toxicity grading was according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life threatening; Grade 5=death. The events that were not given a toxicity grade are categorized as Not Applicable.
Number of Participants Experiencing Primary or Secondary Cardiac Events	From the date of randomization up to 12 months	A cardiac event is classified as a primary cardiac endpoint (PCE) or a secondary cardiac endpoint (SCE). PCE is defined as: cardiac death (cardiac death due to heart failure, myocardial infarction, or arrhythmia;or probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event); severe symptomatic congestive heart failure (CHF) (as per New York Heart Association \[NYHA\] Class III or IV and an absolute decrease in left ventricular ejection fraction \[LVEF\] of more than 10 percentage points from Baseline and to a left ventricular ejection fraction \[LVEF\] value below 50%). SCE is defined as asymptomatic or mildly symptomatic cardiac events (NYHA Class I or II) and a significant decrease in LVEF, defined as an absolute decrease in LVEF of more than 10 percentage points from Baseline and to an LVEF value below 50%.
Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening and Month 12/Early Withdrawal Visit	12-lead ECG measurements were taken at Screening and at study conclusion/withdrawal. The number of participants with normal, abnormal clinically significant (CS), and abnormal not clinically significant (NCS) ECG findings, as classified by the investigator, were summarized. Participants with missing values were categorized as missing. Data for the primary analysis (conducted in 2011) are reported.
Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)	The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The MCS score is a summary score representing overall mental health, which is derived from the 8 domain scores. As with each domain score, the MCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.

Countries

Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Croatia, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Latvia, Lithuania, Mexico, New Zealand, Peru, Philippines, Poland, Russia, Slovakia, South Africa, South Korea, Spain, Ukraine, United Kingdom, United States

Participant flow

Recruitment details

Women with early-stage ErbB2-overexpressing breast cancer who had not been previously treated with trastuzumab were enrolled in this Phase III study. Women who subsequently had no clinical or radiologic evidence of disease were enrolled after completion of primary neoadjuvant/adjuvant chemotherapy.

Pre-assignment details

The study consisted of a Screening Period, a 1-year Treatment Period, and a Follow-up (FU) Period of up to 5 years after the date of study drug withdrawal/completion, for disease status/survival. A total of 3161 eligible participants (par.) (of the 3166 enrolled) were randomized, out of which 3147 par. received at least one dose of study treatment.

Participants by arm

Arm	Count
Lapatinib 1500 mg Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.	1,571
Placebo Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.	1,576
Total	3,147

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Did Not Receive Study Medication	8	6
Overall Study	FU by a Non-Principal Investigator (PI)	2	3
Overall Study	Lost to Follow-up	92	90
Overall Study	Noncompliance with Study Requirements	0	1
Overall Study	Par. Consented to Survival FU Only	3	1
Overall Study	Participant Changed Physician	1	0
Overall Study	Physician Decision	36	32
Overall Study	Protocol Violation	8	3
Overall Study	Seen in FU by a Non-Primary Investigator	1	0
Overall Study	Severe Toxicity	1	0
Overall Study	Site Closed	2	2
Overall Study	Sponsor Decision	2	3
Overall Study	Sponsor Terminated Study	866	990
Overall Study	Started Another Chemotherapy Regimen	0	1
Overall Study	Withdrawal by Subject	235	167
Overall Study	Withdrew Consent During Follow-up	0	5

Baseline characteristics

Characteristic	Placebo	Total	Lapatinib 1500 mg
Age, Continuous	52.3 Years STANDARD_DEVIATION 9.94	52.0 Years STANDARD_DEVIATION 9.92	51.7 Years STANDARD_DEVIATION 9.89
Race/Ethnicity, Customized African American/ African Heritage	62 Participants	115 Participants	53 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	67 Participants	132 Participants	65 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	19 Participants	39 Participants	20 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	229 Participants	465 Participants	236 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	2 Participants	3 Participants	1 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	81 Participants	162 Participants	81 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	11 Participants	16 Participants	5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	11 Participants	14 Participants	3 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	1121 Participants	2247 Participants	1126 Participants
Sex: Female, Male Female	1576 Participants	3147 Participants	1571 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1,443 / 1,573	1,175 / 1,574
serious Total, serious adverse events	99 / 1,573	78 / 1,574

Outcome results

Primary

Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])

DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ; other second primary cancer (excluding squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast); death from any cause without a prior event. Par. who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Par. who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.

Time frame: From randomization until date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause (assessed up to 6 years; 1 year of treatment, 5 years of follow-up [median of 5.3 years for final analysis])

Population: Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of randomized treatment (lapatinib or placebo). Data for the end-of-study analysis (conducted in 2013) are reported.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	Any recurrence or death	252 Participants
Lapatinib 1500 mg	Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	Censored, New Anti-cancer Agent/Radiotherapy	1 Participants
Lapatinib 1500 mg	Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	Censored, Follow-up Ended	1318 Participants
Placebo	Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	Any recurrence or death	290 Participants
Placebo	Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	Censored, New Anti-cancer Agent/Radiotherapy	1 Participants
Placebo	Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	Censored, Follow-up Ended	1285 Participants

p-value: 0.28695% CI: [0.77, 1.08]Log Rank

Secondary

Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)

The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The MCS score is a summary score representing overall mental health, which is derived from the 8 domain scores. As with each domain score, the MCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.

Time frame: Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)

Population: ITT Population (primary analysis \[conducted in 2011\]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Lapatinib 1500 mg	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follw-up, Month 6, n=983, 1074	-2.22 Scores on a scale	Standard Error 0.368
Lapatinib 1500 mg	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follow-up, Month 18, n=834, 889	-2.38 Scores on a scale	Standard Error 0.48
Lapatinib 1500 mg	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Month 12, n=1007, 1204	-2.74 Scores on a scale	Standard Error 0.332
Lapatinib 1500 mg	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follow-up, Month 24, n=807, 824	-2.78 Scores on a scale	Standard Error 0.547
Lapatinib 1500 mg	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follow-up, Month 12, n= 940, 988	-3.08 Scores on a scale	Standard Error 0.393
Lapatinib 1500 mg	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Early inv. product discontinuation, n=289, 120	-6.65 Scores on a scale	Standard Error 0.985
Lapatinib 1500 mg	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Month 6, n=1092, 1283	-2.34 Scores on a scale	Standard Error 0.306
Placebo	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Early inv. product discontinuation, n=289, 120	-8.11 Scores on a scale	Standard Error 1.221
Placebo	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Month 6, n=1092, 1283	-1.74 Scores on a scale	Standard Error 0.297
Placebo	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Month 12, n=1007, 1204	-2.29 Scores on a scale	Standard Error 0.322
Placebo	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follw-up, Month 6, n=983, 1074	-1.87 Scores on a scale	Standard Error 0.361
Placebo	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follow-up, Month 12, n= 940, 988	-2.76 Scores on a scale	Standard Error 0.392
Placebo	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follow-up, Month 18, n=834, 889	-2.08 Scores on a scale	Standard Error 0.475
Placebo	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	Follow-up, Month 24, n=807, 824	-3.05 Scores on a scale	Standard Error 0.554

Secondary

Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)

The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The PCS score is a summary score representing overall physical health, which is derived from the 8 domain scores. As with each domain score, the PCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the last observation carried forward (LOCF) method. The scores were analyzed using an analysis of covariance (ANCOVA) model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.

Time frame: Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)

Population: ITT Population (primary analysis \[conducted in 2011\]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Lapatinib 1500 mg	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Month 12, n=1007, 1204	-0.84 Scores on a scale	Standard Error 0.251
Lapatinib 1500 mg	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 6, n= 983, 1074	-0.53 Scores on a scale	Standard Error 0.287
Lapatinib 1500 mg	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 12, n= 940, 988	-0.88 Scores on a scale	Standard Error 0.29
Lapatinib 1500 mg	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 18, n=834, 889	-0.61 Scores on a scale	Standard Error 0.35
Lapatinib 1500 mg	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 24, n=807, 824	-0.99 Scores on a scale	Standard Error 0.412
Lapatinib 1500 mg	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Early inv. product discontinuation, n=289, 120	-4.39 Scores on a scale	Standard Error 0.712
Lapatinib 1500 mg	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Month 6, n=1092, 1283	-0.78 Scores on a scale	Standard Error 0.217
Placebo	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Month 12, n=1007, 1204	-0.54 Scores on a scale	Standard Error 0.242
Placebo	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 24, n=807, 824	-0.66 Scores on a scale	Standard Error 0.417
Placebo	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 6, n= 983, 1074	-0.87 Scores on a scale	Standard Error 0.281
Placebo	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Month 6, n=1092, 1283	-0.44 Scores on a scale	Standard Error 0.211
Placebo	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 12, n= 940, 988	-0.82 Scores on a scale	Standard Error 0.289
Placebo	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Early inv. product discontinuation, n=289, 120	-4.00 Scores on a scale	Standard Error 0.886
Placebo	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	Follow-up, Month 18, n=834, 889	-0.89 Scores on a scale	Standard Error 0.346

Secondary

Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)

The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH) perceptions, vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). Each domain is scored from 0 (poorer health) to 100 (better health); higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.

Time frame: Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)

Population: ITT Population (primary analysis \[conducted in 2011\]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Early inv. product discontinuation, n=303, 127	-6.96 Scores on a scale	Standard Error 0.882
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 18, n=847, 909	-0.69 Scores on a scale	Standard Error 0.461
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Month 6, n=1132, 1345	-0.52 Scores on a scale	Standard Error 0.235
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Month 12, n=1025, 1234	-0.59 Scores on a scale	Standard Error 0.269
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 6, n=997, 1097	-0.45 Scores on a scale	Standard Error 0.296
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 12, n=955, 1013	-1.11 Scores on a scale	Standard Error 0.317
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 18, n=851, 913	-0.80 Scores on a scale	Standard Error 0.363
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 24, n=818, 845	-1.06 Scores on a scale	Standard Error 0.438
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Early inv. Product discontinuation, n=304, 128	-4.30 Scores on a scale	Standard Error 0.755
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Month 6, n=1130, 1335	-1.37 Scores on a scale	Standard Error 0.276
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Month 12, n=1023, 1230	-1.52 Scores on a scale	Standard Error 0.303
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 6, n=997, 1094	-1.14 Scores on a scale	Standard Error 0.328
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 12, n=955, 1009	-1.78 Scores on a scale	Standard Error 0.344
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 18, n=851, 909	-1.72 Scores on a scale	Standard Error 0.41
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 24, n=818, 842	-1.77 Scores on a scale	Standard Error 0.486
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Month 6, n=1130, 1331	-1.58 Scores on a scale	Standard Error 0.304
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Month 12, n=1024, 1229	-1.75 Scores on a scale	Standard Error 0.338
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 6, n=995, 1094	-1.13 Scores on a scale	Standard Error 0.376
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 12, n=954, 1007	-1.06 Scores on a scale	Standard Error 0.383
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 24, n=817, 840	-1.69 Scores on a scale	Standard Error 0.547
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Early inv. product discontinuation, n=302, 126	-4.92 Scores on a scale	Standard Error 0.95
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Month 6, n=1124, 1319	-1.01 Scores on a scale	Standard Error 0.244
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Month 12, n=1020, 1221	-1.33 Scores on a scale	Standard Error 0.275
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 6, n=994, 1085	-1.25 Scores on a scale	Standard Error 0.314
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 12, n=951, 1002	-1.93 Scores on a scale	Standard Error 0.33
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 18, n=844, 902	-1.28 Scores on a scale	Standard Error 0.397
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 24, n=813, 835	-1.29 Scores on a scale	Standard Error 0.471
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Early inv. product discontinuation, n=299, 124	-5.12 Scores on a scale	Standard Error 0.775
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Month 6, n=1126, 1332	-2.30 Scores on a scale	Standard Error 0.283
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Month 12, n=1022, 1225	-2.49 Scores on a scale	Standard Error 0.309
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 6, n=993, 1090	-1.55 Scores on a scale	Standard Error 0.335
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 12, n=953, 1006	-2.45 Scores on a scale	Standard Error 0.355
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 18, n=848, 906	-1.53 Scores on a scale	Standard Error 0.426
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 24, n=817, 837	-2.03 Scores on a scale	Standard Error 0.501
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Early inv. product discontinuation, n=303, 125	-5.54 Scores on a scale	Standard Error 0.867
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Month 6, n=1138, 1347	-2.34 Scores on a scale	Standard Error 0.299
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Month 12, n=1025, 1234	-2.63 Scores on a scale	Standard Error 0.333
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 6, n=997, 1098	-1.80 Scores on a scale	Standard Error 0.371
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 12, n=957, 1011	-2.47 Scores on a scale	Standard Error 0.383
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 18, n=850, 912	-1.96 Scores on a scale	Standard Error 0.462
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 24, n=819, 843	-2.94 Scores on a scale	Standard Error 0.526
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Early inv. product discontinuation, n=305, 127	-7.05 Scores on a scale	Standard Error 1.017
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Month 6, n=1124, 1328	-1.80 Scores on a scale	Standard Error 0.335
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Month 12, n=1023, 1226	-1.99 Scores on a scale	Standard Error 0.357
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up, Month 6, n=996, 1091	-1.87 Scores on a scale	Standard Error 0.393
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up, Month 12, n=955, 1004	-2.88 Scores on a scale	Standard Error 0.425
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up,Month 18, n=851, 905	-2.47 Scores on a scale	Standard Error 0.509
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up,Month 24, n=818, 839	-2.75 Scores on a scale	Standard Error 0.582
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Early inv. product discontinuation, n=303, 126	-6.85 Scores on a scale	Standard Error 1.02
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Month 6, n=1124, 1332	-1.96 Scores on a scale	Standard Error 0.303
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Month 12, n=1021, 1225	-2.38 Scores on a scale	Standard Error 0.333
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 6, n=993, 1090	-1.92 Scores on a scale	Standard Error 0.367
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 12, n=953, 1006	-2.47 Scores on a scale	Standard Error 0.39
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 18, n=848, 906	-1.91 Scores on a scale	Standard Error 0.469
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 24, n=817, 837	-2.16 Scores on a scale	Standard Error 0.545
Lapatinib 1500 mg	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Early inv. product discontinuation, n=303, 125	-5.96 Scores on a scale	Standard Error 0.964
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 12, n=953, 1006	-2.47 Scores on a scale	Standard Error 0.389
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Month 6, n=1126, 1332	-1.83 Scores on a scale	Standard Error 0.274
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Month 6, n=1124, 1328	-1.69 Scores on a scale	Standard Error 0.325
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Month 6, n=1132, 1345	-0.65 Scores on a scale	Standard Error 0.227
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Month 12, n=1022, 1225	-1.88 Scores on a scale	Standard Error 0.299
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Month 12, n=1025, 1234	-0.91 Scores on a scale	Standard Error 0.26
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Month 6, n=1124, 1332	-1.46 Scores on a scale	Standard Error 0.293
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 6, n=997, 1097	-0.81 Scores on a scale	Standard Error 0.289
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 6, n=993, 1090	-1.61 Scores on a scale	Standard Error 0.328
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 12, n=955, 1013	-1.40 Scores on a scale	Standard Error 0.316
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Month 12, n=1023, 1226	-1.99 Scores on a scale	Standard Error 0.345
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 18, n=851, 913	-1.10 Scores on a scale	Standard Error 0.358
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 12, n=953, 1006	-2.01 Scores on a scale	Standard Error 0.354
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Follow-up, Month 24, n=818, 845	-1.17 Scores on a scale	Standard Error 0.442
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 24, n=817, 837	-2.54 Scores on a scale	Standard Error 0.552
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	PF, Early inv. Product discontinuation, n=304, 128	-4.43 Scores on a scale	Standard Error 0.928
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 18, n=848, 906	-1.25 Scores on a scale	Standard Error 0.421
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Month 6, n=1130, 1335	-0.87 Scores on a scale	Standard Error 0.267
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up, Month 6, n=996, 1091	-1.88 Scores on a scale	Standard Error 0.385
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Month 12, n=1023, 1230	-0.83 Scores on a scale	Standard Error 0.293
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Follow-up, Month 24, n=817, 837	-1.96 Scores on a scale	Standard Error 0.507
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 6, n=997, 1094	-1.45 Scores on a scale	Standard Error 0.322
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Month 12, n=1021, 1225	-2.11 Scores on a scale	Standard Error 0.322
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 12, n=955, 1009	-1.47 Scores on a scale	Standard Error 0.343
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	VT, Early inv. product discontinuation, n=303, 125	-5.78 Scores on a scale	Standard Error 1.067
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 18, n=851, 909	-1.68 Scores on a scale	Standard Error 0.405
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up, Month 12, n=955, 1004	-2.72 Scores on a scale	Standard Error 0.425
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Follow-up, Month 24, n=818, 842	-1.54 Scores on a scale	Standard Error 0.491
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 12, n=954, 1007	-1.19 Scores on a scale	Standard Error 0.382
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RP, Early inv. product discontinuation, n=303, 127	-7.09 Scores on a scale	Standard Error 1.087
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Month 6, n=1138, 1347	-1.42 Scores on a scale	Standard Error 0.289
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Month 6, n=1130, 1331	-1.31 Scores on a scale	Standard Error 0.295
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 18, n=848, 906	-1.58 Scores on a scale	Standard Error 0.464
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Month 12, n=1024, 1229	-1.62 Scores on a scale	Standard Error 0.326
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Month 12, n=1025, 1234	-2.05 Scores on a scale	Standard Error 0.322
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 6, n=995, 1094	-1.35 Scores on a scale	Standard Error 0.368
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up,Month 18, n=851, 905	-2.50 Scores on a scale	Standard Error 0.503
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 18, n=847, 909	-1.07 Scores on a scale	Standard Error 0.455
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 6, n=997, 1098	-1.51 Scores on a scale	Standard Error 0.363
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Follow-up, Month 24, n=817, 840	-1.41 Scores on a scale	Standard Error 0.553
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Follow-up, Month 6, n=993, 1090	-1.70 Scores on a scale	Standard Error 0.36
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	BP, Early inv. product discontinuation, n=302, 126	-4.97 Scores on a scale	Standard Error 1.164
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 12, n=957, 1011	-2.17 Scores on a scale	Standard Error 0.382
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Month 6, n=1124, 1319	-0.34 Scores on a scale	Standard Error 0.236
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Follow-up,Month 24, n=818, 839	-2.95 Scores on a scale	Standard Error 0.589
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Month 12, n=1020, 1221	-0.70 Scores on a scale	Standard Error 0.266
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 18, n=850, 912	-2.01 Scores on a scale	Standard Error 0.456
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 6, n=994, 1085	-1.34 Scores on a scale	Standard Error 0.308
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	MH, Early inv. product discontinuation, n=303, 125	-7.87 Scores on a scale	Standard Error 1.187
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 12, n=951, 1002	-1.48 Scores on a scale	Standard Error 0.329
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Follow-up, Month 24, n=819, 843	-2.75 Scores on a scale	Standard Error 0.532
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 18, n=844, 902	-1.28 Scores on a scale	Standard Error 0.392
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	RE, Early inv. product discontinuation, n=303, 126	-8.00 Scores on a scale	Standard Error 1.258
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Follow-up, Month 24, n=813, 835	-1.02 Scores on a scale	Standard Error 0.476
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	SF, Early inv. product discontinuation, n=305, 127	-7.94 Scores on a scale	Standard Error 1.247
Placebo	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	GH, Early inv. product discontinuation, n=299, 124	-6.30 Scores on a scale	Standard Error 0.965

Secondary

Modified Disease-free Survival (MDFS)

Modified disease recurrence=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause. The date of the event=the earliest date of the occurrence of any of the following events: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including DCIS; death from any cause without a prior event. MDFS was not calculated; data are presented as the number of participants with any recurrence of the initial disease, contralateral breast cancer, or death (disease-free survival) in the subsequent outcome measure table.

Time frame: From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)

Secondary

Number of Participants Experiencing Primary or Secondary Cardiac Events

A cardiac event is classified as a primary cardiac endpoint (PCE) or a secondary cardiac endpoint (SCE). PCE is defined as: cardiac death (cardiac death due to heart failure, myocardial infarction, or arrhythmia;or probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event); severe symptomatic congestive heart failure (CHF) (as per New York Heart Association \[NYHA\] Class III or IV and an absolute decrease in left ventricular ejection fraction \[LVEF\] of more than 10 percentage points from Baseline and to a left ventricular ejection fraction \[LVEF\] value below 50%). SCE is defined as asymptomatic or mildly symptomatic cardiac events (NYHA Class I or II) and a significant decrease in LVEF, defined as an absolute decrease in LVEF of more than 10 percentage points from Baseline and to an LVEF value below 50%.

Time frame: From the date of randomization up to 12 months

Population: Safety Population (SP). Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants Experiencing Primary or Secondary Cardiac Events	PCE, Cardiac death	0 Participants
Lapatinib 1500 mg	Number of Participants Experiencing Primary or Secondary Cardiac Events	PCE, Severe symptomatic CHF	2 Participants
Lapatinib 1500 mg	Number of Participants Experiencing Primary or Secondary Cardiac Events	SCE	6 Participants
Placebo	Number of Participants Experiencing Primary or Secondary Cardiac Events	PCE, Cardiac death	1 Participants
Placebo	Number of Participants Experiencing Primary or Secondary Cardiac Events	PCE, Severe symptomatic CHF	3 Participants
Placebo	Number of Participants Experiencing Primary or Secondary Cardiac Events	SCE	6 Participants

Secondary

Number of Participants Who Died (Overall Survival)

Overall Survival (OS) is defined as the time from randomization until death from any cause. Data are presented as the number of participants who died. For participants who did not die, time to death was censored at the last date the participant was known to be alive.

Time frame: From the date of randomization until death from any cause (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])

Population: ITT Population. Data for the primary analysis (conducted in 2011) are reported.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants Who Died (Overall Survival)	Died	115 Participants
Lapatinib 1500 mg	Number of Participants Who Died (Overall Survival)	Censored, Follow-up Ended	1456 Participants
Placebo	Number of Participants Who Died (Overall Survival)	Died	126 Participants
Placebo	Number of Participants Who Died (Overall Survival)	Censored, Follow-up Ended	1450 Participants

Secondary

Number of Participants With Any Recurrence of the Initial Disease, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])

DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence and contralateral breast cancer, including ductal carcinoma in situ; or death from any cause without a prior event. Participants who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Participants who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.

Time frame: From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)

Population: ITT Population. Data for the end-of-study analysis (conducted in 2013) are reported.

Arm	Measure	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants With Any Recurrence of the Initial Disease, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	184 Participants
Placebo	Number of Participants With Any Recurrence of the Initial Disease, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	231 Participants

Secondary

Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters

The clinical chemistry parameters assessed were: alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), bicarbonate, blood urea nitrogen (BUN), bone alkaline phosphatase (Bone ALP), calcium, chloride, creatinine, creatinine clearance (Cr. Clearance), creatinine clearance estimated (Cr. Clrnc. est.), glucose, potassium, sodium, total bilirubin (Total Bln), total protein, urea, and uric acid. The Baseline (BL) value is the last available pre-treatment result recorded. Any post-Baseline value was based on results recorded at scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) was presented for BL and any post-Baseline (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm.

Time frame: At Baseline and every 6 weeks thereafter up to Month 12/Early Withdrawal Visit

Population: Safety Population (primary analysis \[conducted in 2011\]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed. Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, BL, ref. range high, n=1560, 1566	18 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, BL, ref. range high, n=4, 9	2 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, BL, ref. range low, n=1560, 1566	17 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, APBL, ref. range high, n=1475, 1541	245 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, APBL, ref. range high, n=1465, 1535	35 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, BL, ref. range low, n=52, 46	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, APBL, ref. range low, n=1465, 1535	45 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, APBL, ref. range low, n=1475, 1541	94 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, BL, ref. range high, n=37, 26	7 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, BL, ref. range low, n=4, 9	1 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, BL, ref. range low, n=37, 26	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, BL, ref. range high, n=1567, 1565	13 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, APBL, ref. range high, n=73, 76	10 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, BL, ref. range high, n=1569, 1569	5 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, APBL, ref. range low, n=73, 76	3 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, BL, ref. range low, n=1567, 1565	21 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, BL, ref. range high, n=1569, 1569	55 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, APBL, ref. range high, n=11, 10	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, BL, ref. range low, n=1569, 1569	1 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, APBL, ref. range high, n=1476, 1542	28 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, APBL, ref. range high, n=1478, 1542	271 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, BL, ref. range high, n=52, 46	2 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, APBL, ref. range low, n=1478, 1542	3 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, APBL, ref. range low, n=1476, 1542	54 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, BL, ref. range high, n=1568, 1568	36 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, APBL, ref. range low, n=11, 10	2 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, BL, ref. range low, n=1568, 1568	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, BL, ref. range high, n=1568, 1568	9 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, APBL, ref. range high, n=1475, 1542	51 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, BL, ref. range low, n=1569, 1569	7 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, APBL, ref. range low, n=1475, 1542	11 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, BL, ref. range low, n=1568, 1568	7 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, BL, ref. range high, n=1569, 1569	68 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., BL, ref. range high, n=373, 388	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, BL, ref. range low, n=1569, 1569	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, APBL, ref. range high, n=1477, 1542	29 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, APBL, ref. range high, n=1477, 1542	213 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, APBL, ref. range high, n=102, 108	10 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, APBL, ref. range low, n=1477, 1542	4 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, APBL, ref. range low, n=1477, 1542	24 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, BL, ref. range high, n=1569, 1565	49 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., BL, ref. range low, n=373, 388	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, BL, ref. range low, n=1569, 1565	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., BL, ref. range high, n=1569, 1569	14 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, APBL, ref. range high, n=1478, 1541	260 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, APBL, ref. range high, n=1479, 1542	16 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, APBL, ref. range low, n=1478, 1541	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., BL, ref. range low, n=1569, 1569	1 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, BL, ref. range high, n=36, 33	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., APBL, ref. range high, n=380, 418	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, BL, ref. range low, n=36, 33	4 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., APBL, ref. range high, n=1478, 1542	152 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, APBL, ref. range high, n=60, 71	3 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, APBL, ref. range low, n=1476, 1542	66 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, APBL, ref. range low, n=60, 71	4 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., APBL, ref. range low, n=1478, 1542	4 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, BL, ref. range high, n=63, 56	8 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., APBL, ref. range low, n=380, 418	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, BL, ref. range low, n=63, 56	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, BL, ref. range high, n=1566, 1568	3 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, APBL, ref. range high, n=161, 155	15 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, APBL, ref. range low, n=1479, 1542	22 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, APBL, ref. range low, n=161, 155	6 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, BL, ref. range low, n=1566, 1568	4 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, BL, ref. range high, n=230, 219	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, BL, ref. range high, n=1566, 1569	170 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, BL, ref. range low, n=230, 219	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, APBL, ref. range high, n=1476, 1542	27 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, APBL, ref. range high, n=188, 160	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, APBL, ref. range low, n=102, 108	2 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, APBL, ref. range low, n=188, 160	0 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, APBL, ref. range low, n=1476, 1542	11 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, BL, ref. range high, n=1568, 1565	17 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, BL, ref. range low, n=1566, 1569	31 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, BL, ref. range low, n=1568, 1565	16 Participants
Lapatinib 1500 mg	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, APBL, ref. range high, n=1476, 1542	56 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, BL, ref. range low, n=1568, 1565	14 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, APBL, ref. range high, n=1476, 1542	84 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, APBL, ref. range low, n=1476, 1542	79 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, BL, ref. range high, n=52, 46	2 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, BL, ref. range low, n=52, 46	1 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, APBL, ref. range high, n=102, 108	5 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Chloride, APBL, ref. range low, n=102, 108	5 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, BL, ref. range high, n=1569, 1569	4 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, BL, ref. range low, n=1569, 1569	8 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, APBL, ref. range high, n=1479, 1542	13 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Creatinine, APBL, ref. range low, n=1479, 1542	27 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, BL, ref. range high, n=4, 9	2 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, BL, ref. range low, n=4, 9	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, APBL, ref. range high, n=11, 10	1 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clearance, APBL, ref. range low, n=11, 10	2 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., BL, ref. range high, n=373, 388	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., BL, ref. range low, n=373, 388	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., APBL, ref. range high, n=380, 418	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Cr. Clrnc. est., APBL, ref. range low, n=380, 418	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, BL, ref. range high, n=1566, 1569	143 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, BL, ref. range low, n=1566, 1569	32 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, APBL, ref. range high, n=1475, 1541	329 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Glucose, APBL, ref. range low, n=1475, 1541	94 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, BL, ref. range high, n=1567, 1565	13 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, BL, ref. range low, n=1567, 1565	11 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, APBL, ref. range high, n=1476, 1542	54 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Potassium, APBL, ref. range low, n=1476, 1542	44 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, BL, ref. range high, n=1568, 1568	4 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, BL, ref. range low, n=1568, 1568	9 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, APBL, ref. range high, n=1477, 1542	27 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Sodium, APBL, ref. range low, n=1477, 1542	30 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., BL, ref. range high, n=1569, 1569	19 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., BL, ref. range low, n=1569, 1569	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., APBL, ref. range high, n=1478, 1542	46 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Bln., APBL, ref. range low, n=1478, 1542	3 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, BL, ref. range high, n=1566, 1568	9 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, BL, ref. range low, n=1566, 1568	1 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, APBL, ref. range high, n=1476, 1542	38 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Total Protein, APBL, ref. range low, n=1476, 1542	13 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, BL, ref. range high, n=1560, 1566	19 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, BL, ref. range low, n=1560, 1566	24 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, APBL, ref. range high, n=1465, 1535	48 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Urea, APBL, ref. range low, n=1465, 1535	48 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, BL, ref. range high, n=37, 26	5 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, BL, ref. range low, n=37, 26	1 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, APBL, ref. range high, n=73, 76	12 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Uric acid, APBL, ref. range low, n=73, 76	4 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, BL, ref. range high, n=1569, 1569	78 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, BL, ref. range low, n=1569, 1569	1 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, APBL, ref. range high, n=1478, 1542	141 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALT, APBL, ref. range low, n=1478, 1542	5 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, BL, ref. range high, n=1568, 1568	41 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, BL, ref. range low, n=1568, 1568	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, APBL, ref. range high, n=1475, 1542	70 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Albumin, APBL, ref. range low, n=1475, 1542	8 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, BL, ref. range high, n=1569, 1569	66 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, BL, ref. range low, n=1569, 1569	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, APBL, ref. range high, n=1477, 1542	155 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	ALP, APBL, ref. range low, n=1477, 1542	5 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, BL, ref. range high, n=1569, 1565	59 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, BL, ref. range low, n=1569, 1565	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, APBL, ref. range high, n=1478, 1541	139 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	AST, APBL, ref. range low, n=1478, 1541	3 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, BL, ref. range high, n=36, 33	3 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, BL, ref. range low, n=36, 33	3 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, APBL, ref. range high, n=60, 71	2 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bicarbonate, APBL, ref. range low, n=60, 71	9 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, BL, ref. range high, n=63, 56	4 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, BL, ref. range low, n=63, 56	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, APBL, ref. range high, n=161, 155	17 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	BUN, APBL, ref. range low, n=161, 155	4 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, BL, ref. range high, n=230, 219	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, BL, ref. range low, n=230, 219	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, APBL, ref. range high, n=188, 160	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Bone ALP, APBL, ref. range low, n=188, 160	0 Participants
Placebo	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	Calcium, BL, ref. range high, n=1568, 1565	36 Participants

Secondary

Number of Participants With CNS Recurrence

The number of participants experiencing a CNS recurrence was summarized.

Time frame: From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])

Population: ITT Population. Data for the end-of-study analysis (conducted in 2013) are reported.

Arm	Measure	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants With CNS Recurrence	15 Participants
Placebo	Number of Participants With CNS Recurrence	21 Participants

Secondary

Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters

The hematology parameters assessed were: basophils (Bs) in giga (10\^9) per liter (GI/L) and in percentage (%), eosinophils (Eo) in GI/L and %, hematocrit, hemoglobin, lymphocytes (Lmph) in GI/L and %, monocytes (Mono) in GI/L and %, platelet count, Red Blood Cell (RBC) count, total neutrophil count (TNC) in GI/L and %, and White Blood Cell (WBC) count. The Baseline (BL) value is the last available pre-treatment result recorded. Any post-Baseline value was based on results recorded at any scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) is presented for BL and any post-Baseline (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.

Time frame: At Baseline and every 3 months thereafter up to Month 12/Early Withdrawal Visit

Population: Safety Population (SP): all randomized participants (par.) who received \>=1 dose of randomized treatment. Only those par. available (n=X, X in the category titles) at the specified time points were analyzed. Different par. may have been analyzed for different parameters, so the overall number of par. analyzed reflects everyone in the SP.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, APBL, ref. range high, n=1474, 1538	25 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, BL, ref. range high, n=1560, 1563	20 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, APBL, ref. range low, n=1474, 1538	270 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), BL, ref. range high, n=1557, 1562	5 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), BL, ref. range high, n=1557, 1563	17 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), BL, ref. range low, n=1555, 1563	0 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), BL, ref. range low, n=1557, 1563	47 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), BL, ref. range low, n=1557, 1562	80 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), APBL, ref. range high, n=1469, 1538	38 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, BL, ref. range low, n=1560, 1563	72 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), APBL, ref. range low, n=1469, 1538	115 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), APBL, ref. range high, n=1468, 1538	12 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, BL, ref. range high, n=1559, 1563	18 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), BL, ref. range low, n=1557, 1562	242 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, BL, ref. range low, n=1559, 1563	142 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), APBL, ref. range low, n=1468, 1538	106 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, APBL, ref. range high, n=1471, 1537	42 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, APBL, ref. range high, n=1474, 1538	46 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, APBL, ref. range low, n=1471, 1537	191 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), BL, ref. range high, n=1557, 1562	2 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), BL, ref. range high, n=64, 55	8 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), APBL, ref. range low, n=1466, 1537	7 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), BL, ref. range low, n=64, 55	1 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), BL, ref. range low, n=1557, 1562	236 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), APBL, ref. range high, n=131, 131	17 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, APBL, ref. range low, n=1474, 1538	196 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), APBL, ref. range low, n=131, 131	4 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), APBL, ref. range high, n=1466, 1538	7 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), BL, ref. range high, n=65, 55	7 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), APBL, ref. range high, n=1466, 1537	84 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), BL, ref. range low, n=65, 55	2 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), APBL, ref. range low, n=1466, 1538	425 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), APBL, ref. range high, n=135, 132	16 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, BL, ref. range high, n=1560, 1563	8 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), APBL, ref. range low, n=135, 132	9 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, BL, ref. range high, n=1553, 1559	34 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), BL, ref. range high, n=68, 57	4 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), APBL, ref. range high, n=1466, 1537	7 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), BL, ref. range low, n=68, 57	10 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, BL, ref. range low, n=1553, 1559	21 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), APBL, ref. range high, n=152, 143	14 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, BL, ref. range low, n=1560, 1563	148 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), APBL, ref. range low, n=152, 143	19 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, APBL, ref. range high, n=1473, 153	95 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), BL, ref. range high, n=67, 54	13 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), APBL, ref. range low, n=1466, 1537	322 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), BL, ref. range low, n=67, 54	0 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, APBL, ref. range low, n=1473, 1538	40 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), APBL, ref. range high, n=137, 139	28 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, APBL, ref. range high, n=1474, 1538	32 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), APBL, ref. range low, n=137, 139	6 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, BL, ref. range high, n=1559, 1563	10 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), BL, ref. range high, n=68, 58	7 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), BL, ref. range high, n=1557, 1562	34 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), BL, ref. range low, n=68, 58	5 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, BL, ref. range low, n=1559, 1563	144 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), APBL, ref. range high, n=150, 145	9 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, APBL, ref. range low, n=1474, 1538	295 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), APBL, ref. range low, n=150, 145	19 Participants
Lapatinib 1500 mg	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), BL, ref. range high, n=1555, 1563	0 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), APBL, ref. range low, n=150, 145	12 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), BL, ref. range high, n=1555, 1563	1 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), BL, ref. range low, n=1555, 1563	0 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), APBL, ref. range high, n=1466, 1537	7 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (GI/L), APBL, ref. range low, n=1466, 1537	2 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), BL, ref. range high, n=1557, 1562	35 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), BL, ref. range low, n=1557, 1562	184 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), APBL, ref. range high, n=1466, 1537	75 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (GI/L), APBL, ref. range low, n=1466, 1537	370 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, BL, ref. range high, n=1560, 1563	30 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, BL, ref. range low, n=1560, 1563	96 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, APBL, ref. range high, n=1474, 1538	65 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hematocrit, APBL, ref. range low, n=1474, 1538	145 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, BL, ref. range high, n=1560, 1563	16 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, BL, ref. range low, n=1560, 1563	160 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, APBL, ref. range high, n=1474, 1538	34 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Hemoglobin, APBL, ref. range low, n=1474, 1538	212 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), BL, ref. range high, n=1557, 1562	1 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), BL, ref. range low, n=1557, 1562	89 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), APBL, ref. range high, n=1468, 1538	11 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (GI/L), APBL, ref. range low, n=1468, 1538	100 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), BL, ref. range high, n=1557, 1562	4 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), BL, ref. range low, n=1557, 1562	239 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), APBL, ref. range high, n=1466, 1538	7 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (GI/L), APBL, ref. range low, n=1466, 1538	431 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, BL, ref. range high, n=1553, 1559	33 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, BL, ref. range low, n=1553, 1559	15 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, APBL, ref. range high, n=1473, 153	56 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Platelet count, APBL, ref. range low, n=1473, 1538	37 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, BL, ref. range high, n=1559, 1563	18 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, BL, ref. range low, n=1559, 1563	148 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, APBL, ref. range high, n=1474, 1538	36 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	RBC count, APBL, ref. range low, n=1474, 1538	207 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), BL, ref. range high, n=1557, 1563	15 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), BL, ref. range low, n=1557, 1563	41 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), APBL, ref. range high, n=1469, 1538	53 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (GI/L), APBL, ref. range low, n=1469, 1538	161 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, BL, ref. range high, n=1559, 1563	14 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, BL, ref. range low, n=1559, 1563	104 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, APBL, ref. range high, n=1471, 1537	57 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	WBC count, APBL, ref. range low, n=1471, 1537	198 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), BL, ref. range high, n=64, 55	4 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), BL, ref. range low, n=64, 55	0 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), APBL, ref. range high, n=131, 131	18 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Bs (%), APBL, ref. range low, n=131, 131	1 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), BL, ref. range high, n=65, 55	9 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), BL, ref. range low, n=65, 55	1 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), APBL, ref. range high, n=135, 132	20 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Eo (%), APBL, ref. range low, n=135, 132	4 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), BL, ref. range high, n=68, 57	3 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), BL, ref. range low, n=68, 57	10 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), APBL, ref. range high, n=152, 143	18 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Lmph (%), APBL, ref. range low, n=152, 143	16 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), BL, ref. range high, n=67, 54	11 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), BL, ref. range low, n=67, 54	0 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), APBL, ref. range high, n=137, 139	11 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	Mono (%), APBL, ref. range low, n=137, 139	4 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), BL, ref. range high, n=68, 58	2 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), BL, ref. range low, n=68, 58	4 Participants
Placebo	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	TNC (%), APBL, ref. range high, n=150, 145	10 Participants

Secondary

Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades

Non-laboratory toxicities are defined as adverse events (AEs). The number of partcipants with any treatment-emergent AE of the indicated toxicity grade are summarized. Toxicity grading was according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life threatening; Grade 5=death. The events that were not given a toxicity grade are categorized as Not Applicable.

Time frame: From the first dose of study treatment up to 12 months

Population: Safety Population. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 2	674 Participants
Lapatinib 1500 mg	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 4	21 Participants
Lapatinib 1500 mg	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 1	414 Participants
Lapatinib 1500 mg	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 5	3 Participants
Lapatinib 1500 mg	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Not Applicable	5 Participants
Lapatinib 1500 mg	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 3	333 Participants
Placebo	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Not Applicable	8 Participants
Placebo	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 1	558 Participants
Placebo	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 2	505 Participants
Placebo	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 3	104 Participants
Placebo	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 4	15 Participants
Placebo	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Grade 5	3 Participants

Secondary

Number of Participants With the Indicated Electrocardiogram (ECG) Findings

12-lead ECG measurements were taken at Screening and at study conclusion/withdrawal. The number of participants with normal, abnormal clinically significant (CS), and abnormal not clinically significant (NCS) ECG findings, as classified by the investigator, were summarized. Participants with missing values were categorized as missing. Data for the primary analysis (conducted in 2011) are reported.

Time frame: Screening and Month 12/Early Withdrawal Visit

Population: SP. Only those participants (par.) available at the specified time points were analyzed. Two par. were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, normal, n=1543, 1549	1203 Participants
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, abnormal CS, n=1543, 1549	0 Participants
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, abnormal NCS, n=1543, 1549	339 Participants
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, missing, n=1543, 1549	1 Participants
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, normal, n=1243, 1306	960 Participants
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, abnormal CS, n=1243, 1306	5 Participants
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, abnormal NCS, n=1243, 1306	276 Participants
Lapatinib 1500 mg	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, missing, n=1243, 1306	2 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, missing, n=1243, 1306	1 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, normal, n=1543, 1549	1197 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, normal, n=1243, 1306	979 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, abnormal CS, n=1543, 1549	1 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, abnormal NCS, n=1243, 1306	323 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, abnormal NCS, n=1543, 1549	351 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Conclusion/ Withdrawal, abnormal CS, n=1243, 1306	3 Participants
Placebo	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	Screening, missing, n=1543, 1549	0 Participants

Secondary

Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)

Distant recurrence (metastatic disease) is defined as a tumor in any area of the body not including those defined as local or regional recurrence. Sites of distant recurrence include: skin, subcutaneous tissue, and lymph nodes (excluding those described for local and regional recurrence); bone marrow; skeletal; lungs and pleural; ascites and pleural effusions; liver and other viscera; and central nervous system (CNS). Time to distant recurrence is defined as the interval between the date of randomization and the date of the first occurrence of a distant recurrence.

Time frame: From the date of randomization until the date of the first occurrence of a distant recurrence (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])

Population: ITT Population. Data for the primary analysis (conducted in 2011) are reported.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	18 Months	4.3 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	3 Years	8.1 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	1Year	2.9 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	4 Years	9.3 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	2 Years	5.9 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	5 Years	NA Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	6 Months	0.9 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	5 Years	14.2 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	6 Months	1.9 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	1Year	3.8 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	18 Months	6.0 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	2 Years	7.2 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	3 Years	9.1 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	4 Years	11.1 Percentage of participants

Secondary

Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)

Recurrence is defined as experiencing a recurrence of initial disease or contralateral breast cancer after randomization. Time to first recurrence is defined as the interval between the date of randomization and the date of the first occurrence of an objective disease recurrence or contralateral breast cancer. Time to first recurrence included the first occurrence at one of the following sites as an event: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ (DCIS).

Time frame: From the date of randomization until the date of the first occurrence of an objective disease recurrence or contralateral breast cancer (assessed up to 6 years; 1 year of treatment and 5.3 years of follow-up [median of 5 years for final analysis])

Population: ITT Population. Data for the primary analysis (conducted in 2011) are reported.

Arm	Measure	Group	Value (NUMBER)
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	1Year	3.7 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	2 Years	7.7 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	6 Months	1.3 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	3 Years	10.6 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	18 Months	5.6 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	4 Years	13.3 Percentage of participants
Lapatinib 1500 mg	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	5 Years	NA Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	4 Years	15.8 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	5 Years	24.9 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	6 Months	2.8 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	1Year	5.4 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	18 Months	8.2 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	2 Years	9.9 Percentage of participants
Placebo	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	3 Years	12.6 Percentage of participants

Secondary

Time to Central Nervous System (CNS) Recurrence

Time to CNS recurrence is defined as the interval between the date of randomization and the date of the occurrence of a CNS recurrence if noted as part of the participant's first recurrence. Time to CNS recurrence was not calculated; data are presented as the number of participants with CNS recurrence in the subsequent outcome measure table.

Source: ClinicalTrials.gov · Data processed: Mar 24, 2026

Tykerb Evaluation After Chemotherapy (TEACH): Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])

Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)

Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)

Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)

Modified Disease-free Survival (MDFS)

Number of Participants Experiencing Primary or Secondary Cardiac Events

Number of Participants Who Died (Overall Survival)

Number of Participants With Any Recurrence of the Initial Disease, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])

Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters

Number of Participants With CNS Recurrence

Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters

Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades

Number of Participants With the Indicated Electrocardiogram (ECG) Findings

Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)

Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)

Time to Central Nervous System (CNS) Recurrence