Neoplasms, Head and Neck
Conditions
Keywords
Cancer of the Head and Neck, Neck cancer, Adjuvant, Head and neck cancer, High-risk head and neck cancer, Post-surgery, Head cancer
Brief summary
This is a randomised, double-blind, placebo-controlled, multicentre, global Phase III trial comparing the efficacy of adjuvant oral lapatinib versus placebo in high-risk subjects with head and neck cancer following surgery. Lapatinib or placebo will be administered post-operatively in combination with chemoradiotherapy followed by maintenance with lapatinib or placebo for 1 year. The primary goal is to determine if lapatinib is effective at reducing the recurrence of the disease in these high-risk patients.
Detailed description
A Randomised, Double-Blind, Placebo-Controlled, Multi-centre, Phase III Study of Post-Operative Adjuvant Lapatinib or Placebo and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib or Placebo Monotherapy in High-Risk Subjects with Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Interventions
DRUGLapatinib
Dual ErbB1/2 inhibitor
RADIATIONChemoradiation
Radiation plus platinum based chemotherapy
OTHERPlacebo
Placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to sign a written informed consent. * Histologically confirmed diagnosis of SCCHN of one of the following sites: oral cavity, oropharynx, hypopharynx and larynx. * Pathological Stage II, III or IVa (according to AJCC cancer staging criteria \[Green, 2002\]) with no evidence of gross residual disease, and at least one of the following high risk factors by pathology: * Extracapsular extension of nodal disease * Positive resection margin (5 mm or less) * Primary surgery with a curative intent completed within 4-6 weeks (and no later than 7 weeks) prior to randomization. The extent of surgical resection will follow accepted criteria for adequate excision \[Helliwell, 2005\]. Surgical margins are divided into 'mucosal' and 'deep', and for each category the resection margin (R) is classified as: * Clear : (R0) \> 5mm. * Close: (R1) 1 - 5mm. * Involved: (R2) \<1mm * Complete recovery from the surgical procedure allowing for appropriate radiotherapy. Radiation therapy is required to start as soon as adequate healing has occurred. This is normally around 4-6 weeks but no later than 9 weeks after surgery. * Adequate tumour specimen from archived or resected tissue must be available for IHC evaluation of ErbB1 expression levels in a central laboratory and subsequent biomarker analysis. * Male or female, between 18 and 70 years of age \[Bourhis, 2006\]. Criteria for female subjects or female partners of male subjects: Non-child-bearing potential (i.e., a woman with functioning ovaries who has a current documented tubal ligation or hysterectomy or a woman who is menopausal); or Child-bearing potential (i.e. a woman with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (even severe), women who are perimenopausal and young women who have begun to menstruate), who have a negative serum pregnancy test at screening, and agree to one of the following: Complete abstinence from intercourse from the time of the screening pregnancy test until 28 days after the final dose of test article; or Consistent and correct use of one of the following acceptable methods of birth control: Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; or Oral contraceptives (either combined or progestogen only), or Injectable progestogen-only contraceptives or Implants of levonorgestrel, or Any intrauterine device with a documented failure rate of less than 1% per year; or Barrier methods (e.g. condoms, diaphragms, caps) only if used in combination with one of the above acceptable methods. * ECOG performance status 0, 1 or 2 * Adequate haematology, renal and hepatic function Absolute neutrophil count ≥ 1,500/μL, platelets ≥ 100,000/μL Haemoglobin ≥ 9 gm/dL (5mmol/L) Calculated creatinine clearance ≥60 ml/min as determined by the modified method of Cockcroft and Gault. Aspartate (AST) and alanine transaminase (ALT) less than 3 times the upper limit of the normal range (ULN). Total bilirubin ≤ 2.0 mg/dL * Left ventricular ejection fraction (LVEF) above the lower limits of the institutional normal range as measured by ECHO (if ECHO cannot be performed or if the Investigator feels it is not conclusive to evaluate LVEF, then a MUGA scan should be performed). * Able to swallow and retain tablets whole or swallow a suspension of tablets dissolved in water at study inclusion. The use of feeding tube is optional. If necessary, the suspension may be administered via percutaneous endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (J- Tube), or a nasogastric tube (NG or Dobhoff type tube). * Life expectancy of at least 6 months in the best judgement of the investigator * Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
Exclusion criteria
* Nasopharyngeal, paranasal sinuses or nasal cavity tumours * Head and neck cancer with histology other than squamous cell carcinoma. * Evidence of distant metastases or gross post-operative residual disease. * Evidence of second primary tumour. * Any prior or current anticancer treatment of any kind - except the primary surgical resection. This will include but is not limited to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior radiotherapy or use of any investigational agent. * Concurrent treatment with an investigational agent or participation in another clinical trial. * Concurrent use of CYP3A4 inducers or inhibitors while on lapatinib/placebo. A standard 3 to 5 day course of dexamethasone for the prevention of cisplatin induced nausea and vomiting is permitted. In addition glucocorticoid daily doses (oral) 1.5mg dexamethasone (or equivalent) are allowed. * Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; * Pregnant or lactating females * History of another malignancy within the last 5 years, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma. History of non-invasive lesion or in-situ carcinoma, that was successfully treated with surgery, photodynamics or laser, will be permitted; * Peripheral neuropathy ≥ grade 2 * Mal-absorption syndrome, disease significantly affecting GI function, or major resection of the stomach or bowel, that could affect absorption of lapatinib. * History of allergic reactions to relevant diuretics or anti-emetics (e.g 5-HT3 antagonists) to be administered with cisplatin chemotherapy * History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib * The investigator considers the subject unfit for the study as a result of the medical interview, physical examinations, or screening investigations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | From randomization until the earliest date of disease recurrence or death due to any cause (average of 101 study weeks) | DFS is defined as the time from randomization until the earliest date of disease recurrence (evidence of local, regional, or distant disease progression, second primary tumor) or death due to any cause. Disease recurrence was based on the assessments from the blinded, independent reviewer (radiological and clinical). Participants who initiated alternative anti-cancer therapy prior to disease recurrence or death were treated as censored at the last assessment prior to the time of this initiation. For participants whose disease did not recur or who did not die, DFS was censored at the time of the last independently assessed radiological scan (where initiation of alternative anti-cancer therapy had not commenced). Participants who missed two or more consecutive disease assessments were censored at the last assessment prior to the missed assessments. Participants considered to have malignant disease at Baseline were censored at the time of randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Specific Survival (DSS) | From randomization until death due to head and neck cancer (average of 131 study weeks) | DSS is defined as the time from randomization until death due to head and neck cancer. Participants whose death was not related to the disease under study were treated as competing risks at the time death occured. Participants who were alive were censored at the time of their last visit. |
| Time to Locoregional Recurrence (TTLR) | From randomization until thefirst occurrence that local and/or regional recurrence is documented or the date of censor (average of 101 study weeks) | TTLR is defined as the time from randomization until the first occurrence that local and/or regional recurrence is documented or the date of censor. Local relapse is defined as recurrent cancer in the primary tumor bed not clearly attributable to a second primary neoplasm. Regional relapse is defined as recurrent cancer in the neck not clearly attributable to a second primary neoplasm. All other events prior to locoregional recurrence were treated as competing risks at the time they occured. All other participants were treated as censored at the time of their last disease assessment. Participants with malignant disease at Baseline according to the independent review were censored at the time of randomization for the analysis of independently reviewed data. |
| Time to Distant Relapse (TTDR) | From randomization until the first documented occurrence that distant relapse is documented (average of 101 study weeks) | TTDR is defined as the time from randomization until the first occurrence that distant relapse is documented. Distant relapse is defined as clear evidence of distant metastases (lung, bone, brain, etc.). Metastasis is defined as the spread of a cancer from one organ or part to another non-adjacent organ or part. All other events prior to a distant relapse were treated as competing risks at the time they occured. All other participants were treated as censored at the time of their last disease assessment. Participants with malignant disease at Baseline according to the independent review were censored at the time of randomization for the analysis of independently reviewed data. |
| Number of Participants With a Second Primary Tumor | From randomization until development of second primary tumor or within 28 days of first recurrence (average of 101 study weeks) | Participants who developed a second primary tumor at the time of the first recurrence or within 28 days of the first recurrence were measured. The criteria for a second primary tumor are as follows: a distinct lesion separated from the primary tumor site by \>2 centimeters of normal epithelium; or a new cancer with different histology; or any cancer, regardless of site, occurring \>=3 years after initial treatment. Participants with baseline disease were included in the denominator when calculating the percentage. |
| Extent of Exposure | From randomization until end of 1year maintenance treatment (average of 63 study weeks) | Extent of exposure is defined as the duration of treatment administered during the study. The mean duration of treatment is calculated as the number of days between the start of treatment and the end of treatment inclusive (i.e., treatment stop date minus treatment start date + 1). Participants were counted in a treatment phase (monotherapy, chemoradiotherapy, and maintenance) if they had received any dose in that phase. Participants randomized to placebo who received \>=1 dose of lapatinib in error were included in the lapatinib arm. |
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From the first dose of lapatinib/placebo until 5 days after the last dose (average of 141 study weeks) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of non-serious AEs occurring at a frequency threshold of 5% and SAEs. |
| Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | From Baseline (within 8 weeks prior to randomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64) | Data are summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI CTC version 3.0) toxicity grades. Data are reported as the number of participants who had a grade 3 (G3) or grade 4 (G4) toxicity for the indicated chemistry parameters, where G3 indicates a severe toxicity and G4 indicates a life-threatening toxicity. Clinical chemistry parameters included: albumin, alkaline phosphatase (AP), alanine amino transferase (ALT), aspartate amino transeferase (AST), total bilirubin (TB), calcium, carbon dioxide content/bicarbonate (CO2/HCO3), creatinine, glucose, potassium, and sodium. The worst-case on-therapy visit includes any scheduled or unscheduled post-Baseline visit. |
| Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | From Baseline (within 8 weeks prior torandomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64) | Data are summarized using the NCI CTC version 3.0 toxicity grades. Data are reported as the number of participants who had a grade 3 (G3) or grade 4 (G4) toxicity for the indicated hematological parameters, where G3 indicates a severe toxicity and G4 indicates a life-threatening toxicity. The worst-case on-therapy visit includes any scheduled or unscheduled post-Baseline visit. Hematology parameter included: hemoglobin, total neutrophils (TN), platelet count (PC), and White Blood Cell (WBC) count. |
| Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | From 180 days after completion of radiation until the last follow-up/withdrawal visit (average of 64 study weeks) | Late radiation morbidity event data are summarized as the number of participants with late radiation morbidity events per system organ class (SOC). Late radiation effects are defined as those that first occur 90 days or more after the initiation of radiation therapy. |
| Overall Survival (OS) | From randomization until death due to any cause (average of 131 study weeks) | OS is defined as the time from randomization until death due to any cause. For participants who did not die, the time to death was censored at the time of last visit/contact. |
| Change From Baseline in Heart Rate at the Indicated Time Points | Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from IP (up to Study Week 64) | Heart rate (HR) was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in Body Temperature at the Indicated Time Points | Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from IP (up to Study Week 64) | Body temperature was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in Body Weight at the Indicated Time Points | Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from IP (up to Study Week 64) | Body weight was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Baseline (BL; within 8 weeks prior to randomization [Day 1]), End of CRT, Maintenance Week 56, Withdrawal from IP, and at any time Post-Baseline (up to Study Week 64) | A 12-lead ECG was recorded at Baseline, at the end of the CRT, at Maintenance Week 56, at withdrawal from IP, and at anytime post-baseline. Data are presented as clinically significant (CS) or not clinically significant (NCS) abnormal findings. The study investigator determined if an abnormal ECG finding was CS or NCS. |
| Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | From Baseline (BL; within 8 weeks prior to randomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64) | The Eastern Cooperative Oncology Group (ECOG) performance status scales and grades/criteria are used by doctors and researchers to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead. |
| Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | From randomization until the last follow-up/withdrawal visit (up to 62 study weeks) | Change from Baseline in quality of life status was assessed using the FACT-H&N questionnaire, which is designed to measure multidimensional quality of life in participants with head and neck cancer. Change from Baseline was analyzed using parametric analysis of covariance (with the Baseline value as a covariate). The FACT-H&N questionnaire contains 39 items (27 general questions and 12 head and neck cancer-specific items) covering 4 dimensions and 1 subscale: physical well-being, social/family well-being, emotional well-being, functional well-being, and a head and neck cancer subscale. Possible subscale scores range from 0 to 36. Higher scores represent better quality of life. Data were adjusted for participant-reported quality of life scores at Baseline. |
| Change From Baseline in Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale | From randomization until the last follow-up/withdrawal visit (up to 62 study weeks) | Change from Baseline in quality of life status was assessed using the EQ-5D scale, a 5-item health status measure and a visual analog rating scale. Change from Baseline was analyzed using parametric analysis of covariance (with the Baseline value as a covariate). The EQ-5D is a generic measure of self-reported health outcomes that is applicable to a wide range of health conditions and treatments. The EQ-5D covers health status in 5 domains (3 questions each): mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each item is scored as follows: 1, no problems; 2, some moderate problems; 3, extreme problems. The possible EQ-5D index utility values range from 0.594 to 1, and the thermometer score ranges from 0 to 100. Higher scores represent better quality of life. Data were adjusted for participant-reported quality of life scores at Baseline. |
| Number of Participants With the Indicated Biomarker Expression Status | Baseline (BL; within 8 weeks prior to randomization [Day 1]) (up to Study Week 1) | Biomarkers (which influence clinical response) assessed from tumor tissues included P16, Human Papilloma virus (HPV), and Epidermal Growth Factor Receptor (EGFR)/Epidermal Growth Factor Receptor 1 (ErbB1). Biomarker expression is presented as positive, negative, or unknown. Participants in the ErbB1-positive category include those with results of positive or strongly positive. |
| Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | From the end of the CRT until the last follow-up visit (average of 141 study weeks) | LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart with each contraction. LVEF was assessed using echocardiogram (ECHO: a test of the action of the heart using ultrasound waves to produce a visual display, for the diagnosis or monitoring of heart disease ) and multigated acqusition scans (MUGA scan: a noninvasive diagnostic test used to evaluate the pumping function of the ventricles). Data from the ECHO and MUGA scans were combined, and the absolute change from Baseline (Abs) data are presented according to the following categories: No change or any increase, 0-\<10% decrease, 10-19% decrease, \>=20% decrease, \>=10% decrease and \>=the Lower Limit of Normal (LLN), \>=10% decrease and below LLN, \>=20% decrease and \>=LLN, or \>=20% decrease and below LLN. The relative percent change from Baseline (Rel) data are presented according to the following categories: \>=20% decrease and \>=LLN and \>=20% decrease and below LLN. |
| Change From Baseline in Blood Pressure at the Indicated Time Points | Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from investigational product (IP; up to Study Week 64) | Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
Countries
Argentina, Austria, Canada, China, Croatia, Czechia, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Italy, Philippines, Russia, Slovakia, Spain, Thailand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m\^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner. | 342 |
| Lapatinib 1500 mg Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m\^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner. | 346 |
| Total | 688 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Cognitive Disturbance | 1 | 0 |
| Overall Study | Death | 115 | 111 |
| Overall Study | Disease Progression | 0 | 2 |
| Overall Study | Fatigue | 1 | 0 |
| Overall Study | Lost to Follow-up | 26 | 20 |
| Overall Study | Non-compliance by Participants | 1 | 0 |
| Overall Study | Physician Decision | 3 | 7 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor Terminated Study | 161 | 167 |
| Overall Study | Withdrawal by Subject | 34 | 38 |
Baseline characteristics
| Characteristic | Placebo | Lapatinib 1500 mg | Total |
|---|---|---|---|
| Age, Continuous | 53.7 Years STANDARD_DEVIATION 9.85 | 53.8 Years STANDARD_DEVIATION 8.38 | 53.8 Years STANDARD_DEVIATION 9.14 |
| Race/Ethnicity, Customized African American/African Heritage | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 61 Participants | 53 Participants | 114 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 41 Participants | 47 Participants | 88 Participants |
| Race/Ethnicity, Customized Asian - Mixed Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 19 Participants | 23 Participants | 42 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 219 Participants | 219 Participants | 438 Participants |
| Sex: Female, Male Female | 55 Participants | 60 Participants | 115 Participants |
| Sex: Female, Male Male | 287 Participants | 286 Participants | 573 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 321 / 336 | 337 / 349 |
| serious Total, serious adverse events | 133 / 336 | 169 / 349 |
Outcome results
Primary
Disease Free Survival (DFS)
DFS is defined as the time from randomization until the earliest date of disease recurrence (evidence of local, regional, or distant disease progression, second primary tumor) or death due to any cause. Disease recurrence was based on the assessments from the blinded, independent reviewer (radiological and clinical). Participants who initiated alternative anti-cancer therapy prior to disease recurrence or death were treated as censored at the last assessment prior to the time of this initiation. For participants whose disease did not recur or who did not die, DFS was censored at the time of the last independently assessed radiological scan (where initiation of alternative anti-cancer therapy had not commenced). Participants who missed two or more consecutive disease assessments were censored at the last assessment prior to the missed assessments. Participants considered to have malignant disease at Baseline were censored at the time of randomization.
Time frame: From randomization until the earliest date of disease recurrence or death due to any cause (average of 101 study weeks)
Population: Intent-to-Treat (ITT) Population: all participants who were randomized to study treatment, irrespective of whether they actually received study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Disease Free Survival (DFS) | NA Months |
| Lapatinib 1500 mg | Disease Free Survival (DFS) | 53.6 Months |
p-value: 0.2251Non-stratified log-rank test
p-value: 0.4502Non-stratified log-rank test
95% CI: [0.85, 1.43]
Secondary
Change From Baseline in Blood Pressure at the Indicated Time Points
Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from investigational product (IP; up to Study Week 64)
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). 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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 8, n=280, 279 | -2.80 Millimeters of mercury (mmHg) | Standard Deviation 14.137 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 2, n=303, 327 | -2.40 Millimeters of mercury (mmHg) | Standard Deviation 13.815 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 3, n=310, 319 | -2.64 Millimeters of mercury (mmHg) | Standard Deviation 14.784 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 4, n=312, 319 | -4.32 Millimeters of mercury (mmHg) | Standard Deviation 15.414 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 5, n=302, 303 | -4.05 Millimeters of mercury (mmHg) | Standard Deviation 15.49 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 6, n=307, 307 | -4.70 Millimeters of mercury (mmHg) | Standard Deviation 15.571 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 7, n=282, 289 | -4.06 Millimeters of mercury (mmHg) | Standard Deviation 14.774 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, End of CRT, n=304, 310 | -4.79 Millimeters of mercury (mmHg) | Standard Deviation 15.216 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 1, n=312, 339 | -0.29 Millimeters of mercury (mmHg) | Standard Deviation 14.153 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 16, n=257, 270 | -2.86 Millimeters of mercury (mmHg) | Standard Deviation 15.251 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 24, n=234, 252 | -3.44 Millimeters of mercury (mmHg) | Standard Deviation 15.918 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 32, n=212, 237 | -1.71 Millimeters of mercury (mmHg) | Standard Deviation 14.936 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 40, n=202, 222 | -1.76 Millimeters of mercury (mmHg) | Standard Deviation 14.979 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 48, n=199, 210 | -1.57 Millimeters of mercury (mmHg) | Standard Deviation 15.531 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 56, n=188, 204 | -1.53 Millimeters of mercury (mmHg) | Standard Deviation 13.942 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Withdrawal from IP, n=99, 84 | -2.54 Millimeters of mercury (mmHg) | Standard Deviation 15.746 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 1, n=312, 339 | -0.07 Millimeters of mercury (mmHg) | Standard Deviation 9.214 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 2, n=303, 327 | -0.81 Millimeters of mercury (mmHg) | Standard Deviation 8.69 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 3, n=310, 319 | -0.46 Millimeters of mercury (mmHg) | Standard Deviation 9.245 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 4, n=312, 319 | -2.54 Millimeters of mercury (mmHg) | Standard Deviation 9.929 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 5, n=302, 303 | -1.38 Millimeters of mercury (mmHg) | Standard Deviation 10.1 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 6, n=307, 307 | -1.85 Millimeters of mercury (mmHg) | Standard Deviation 10.673 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 7, n=282, 289 | -1.73 Millimeters of mercury (mmHg) | Standard Deviation 11.095 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, End of CRT, n=304, 310 | -1.97 Millimeters of mercury (mmHg) | Standard Deviation 10.224 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 8, n=280, 279 | -0.80 Millimeters of mercury (mmHg) | Standard Deviation 9.598 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 16, n=257, 270 | -0.36 Millimeters of mercury (mmHg) | Standard Deviation 9.98 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 24, n=234, 252 | -1.26 Millimeters of mercury (mmHg) | Standard Deviation 9.956 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 32, n=212, 237 | -0.38 Millimeters of mercury (mmHg) | Standard Deviation 9.677 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 40, n=202, 222 | -0.69 Millimeters of mercury (mmHg) | Standard Deviation 9.809 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 48, n=199, 210 | 0.34 Millimeters of mercury (mmHg) | Standard Deviation 10.797 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 56, n=188, 204 | 0.20 Millimeters of mercury (mmHg) | Standard Deviation 9.721 |
| Placebo | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Withdrawal from IP, n=99, 84 | -0.27 Millimeters of mercury (mmHg) | Standard Deviation 10.256 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Withdrawal from IP, n=99, 84 | -0.85 Millimeters of mercury (mmHg) | Standard Deviation 11.806 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 1, n=312, 339 | 1.24 Millimeters of mercury (mmHg) | Standard Deviation 14.273 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 1, n=312, 339 | 0.63 Millimeters of mercury (mmHg) | Standard Deviation 9.719 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 2, n=303, 327 | -1.56 Millimeters of mercury (mmHg) | Standard Deviation 16.415 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 8, n=280, 279 | -1.17 Millimeters of mercury (mmHg) | Standard Deviation 9.877 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 3, n=310, 319 | -1.62 Millimeters of mercury (mmHg) | Standard Deviation 15.046 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 2, n=303, 327 | -0.24 Millimeters of mercury (mmHg) | Standard Deviation 9.933 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 4, n=312, 319 | -2.63 Millimeters of mercury (mmHg) | Standard Deviation 17.044 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 40, n=202, 222 | -0.69 Millimeters of mercury (mmHg) | Standard Deviation 11.54 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 5, n=302, 303 | -3.09 Millimeters of mercury (mmHg) | Standard Deviation 16.472 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 3, n=310, 319 | -0.68 Millimeters of mercury (mmHg) | Standard Deviation 9.704 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 6, n=307, 307 | -4.07 Millimeters of mercury (mmHg) | Standard Deviation 15.726 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 16, n=257, 270 | -0.98 Millimeters of mercury (mmHg) | Standard Deviation 9.527 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Week 7, n=282, 289 | -4.86 Millimeters of mercury (mmHg) | Standard Deviation 17.046 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 4, n=312, 319 | -2.03 Millimeters of mercury (mmHg) | Standard Deviation 9.797 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, End of CRT, n=304, 310 | -4.69 Millimeters of mercury (mmHg) | Standard Deviation 16.692 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 56, n=188, 204 | -0.47 Millimeters of mercury (mmHg) | Standard Deviation 10.475 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 8, n=280, 279 | -3.58 Millimeters of mercury (mmHg) | Standard Deviation 15.03 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 5, n=302, 303 | -1.60 Millimeters of mercury (mmHg) | Standard Deviation 9.679 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 16, n=257, 270 | -2.44 Millimeters of mercury (mmHg) | Standard Deviation 15.718 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 24, n=234, 252 | -1.65 Millimeters of mercury (mmHg) | Standard Deviation 9.842 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 24, n=234, 252 | -2.48 Millimeters of mercury (mmHg) | Standard Deviation 15.793 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 6, n=307, 307 | -2.37 Millimeters of mercury (mmHg) | Standard Deviation 9.514 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 32, n=212, 237 | -2.55 Millimeters of mercury (mmHg) | Standard Deviation 15.47 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 48, n=199, 210 | -0.56 Millimeters of mercury (mmHg) | Standard Deviation 10.057 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 40, n=202, 222 | -1.84 Millimeters of mercury (mmHg) | Standard Deviation 17.358 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, Week 7, n=282, 289 | -2.93 Millimeters of mercury (mmHg) | Standard Deviation 9.402 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 48, n=199, 210 | -1.79 Millimeters of mercury (mmHg) | Standard Deviation 15.7 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, MW 32, n=212, 237 | -1.34 Millimeters of mercury (mmHg) | Standard Deviation 9.929 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, MW 56, n=188, 204 | -1.64 Millimeters of mercury (mmHg) | Standard Deviation 15.878 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | DBP, End of CRT, n=304, 310 | -2.11 Millimeters of mercury (mmHg) | Standard Deviation 10.117 |
| Lapatinib 1500 mg | Change From Baseline in Blood Pressure at the Indicated Time Points | SBP, Withdrawal from IP, n=99, 84 | -1.38 Millimeters of mercury (mmHg) | Standard Deviation 17.895 |
Secondary
Change From Baseline in Body Temperature at the Indicated Time Points
Body temperature was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from IP (up to Study Week 64)
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). 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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Week 1, n=308, 331 | -0.03 Degrees Centigrade | Standard Deviation 0.42 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Week 2, n=303, 321 | -0.01 Degrees Centigrade | Standard Deviation 0.492 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Week 3, n=308, 315 | 0.02 Degrees Centigrade | Standard Deviation 0.504 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Week 4, n=306, 317 | 0.02 Degrees Centigrade | Standard Deviation 0.511 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Week 5, n=300, 303 | -0.00 Degrees Centigrade | Standard Deviation 0.514 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Week 6, n=301, 302 | 0.06 Degrees Centigrade | Standard Deviation 0.586 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Week 7, n=277, 288 | 0.02 Degrees Centigrade | Standard Deviation 0.526 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | End of CRT, n=297, 305 | 0.04 Degrees Centigrade | Standard Deviation 0.545 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | MW 8, n=274, 273 | 0.02 Degrees Centigrade | Standard Deviation 0.529 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | MW 16, n=253, 263 | -0.02 Degrees Centigrade | Standard Deviation 0.525 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | MW 24, n=227, 244 | -0.03 Degrees Centigrade | Standard Deviation 0.516 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | MW 32, n=207, 235 | -0.04 Degrees Centigrade | Standard Deviation 0.559 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | MW 40, n=199, 219 | -0.04 Degrees Centigrade | Standard Deviation 0.542 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | MW 48, n=195, 205 | -0.02 Degrees Centigrade | Standard Deviation 0.645 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | MW 56, n=184, 200 | -0.01 Degrees Centigrade | Standard Deviation 0.563 |
| Placebo | Change From Baseline in Body Temperature at the Indicated Time Points | Withdrawal from IP, n=97, 78 | 0.00 Degrees Centigrade | Standard Deviation 0.562 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Withdrawal from IP, n=97, 78 | 0.03 Degrees Centigrade | Standard Deviation 0.419 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 1, n=308, 331 | -0.01 Degrees Centigrade | Standard Deviation 0.436 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | MW 8, n=274, 273 | 0.01 Degrees Centigrade | Standard Deviation 0.442 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 2, n=303, 321 | 0.01 Degrees Centigrade | Standard Deviation 0.41 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | MW 40, n=199, 219 | -0.00 Degrees Centigrade | Standard Deviation 0.429 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 3, n=308, 315 | 0.01 Degrees Centigrade | Standard Deviation 0.431 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | MW 16, n=253, 263 | -0.03 Degrees Centigrade | Standard Deviation 0.4 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 4, n=306, 317 | 0.04 Degrees Centigrade | Standard Deviation 0.494 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | MW 56, n=184, 200 | -0.02 Degrees Centigrade | Standard Deviation 0.466 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 5, n=300, 303 | 0.03 Degrees Centigrade | Standard Deviation 0.416 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | MW 24, n=227, 244 | 0.04 Degrees Centigrade | Standard Deviation 0.425 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 6, n=301, 302 | 0.02 Degrees Centigrade | Standard Deviation 0.54 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | MW 48, n=195, 205 | -0.01 Degrees Centigrade | Standard Deviation 0.464 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 7, n=277, 288 | 0.06 Degrees Centigrade | Standard Deviation 0.507 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | MW 32, n=207, 235 | -0.02 Degrees Centigrade | Standard Deviation 0.453 |
| Lapatinib 1500 mg | Change From Baseline in Body Temperature at the Indicated Time Points | End of CRT, n=297, 305 | 0.03 Degrees Centigrade | Standard Deviation 0.469 |
Secondary
Change From Baseline in Body Weight at the Indicated Time Points
Body weight was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from IP (up to Study Week 64)
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). 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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Week 1, n=317, 343 | 0.28 Kilograms | Standard Deviation 2.301 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Week 2, n=314, 336 | -0.39 Kilograms | Standard Deviation 2.32 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Week 3, n=319, 328 | -1.01 Kilograms | Standard Deviation 2.638 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Week 4, n=316, 324 | -1.74 Kilograms | Standard Deviation 3.116 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Week 5, n=307, 309 | -2.46 Kilograms | Standard Deviation 3.424 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Week 6, n=314, 307 | -3.22 Kilograms | Standard Deviation 3.868 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Week 7, n=290, 297 | -4.21 Kilograms | Standard Deviation 4.072 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | End of CRT, n=309, 311 | -4.54 Kilograms | Standard Deviation 4.566 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | MW 8, n=287, 287 | -4.56 Kilograms | Standard Deviation 5.851 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | MW 16, n=257, 275 | -4.31 Kilograms | Standard Deviation 6.521 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | MW 24, n=236, 252 | -4.26 Kilograms | Standard Deviation 7.251 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | MW 32, n=220, 241 | -4.17 Kilograms | Standard Deviation 7.685 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | MW 40, n=208, 224 | -3.63 Kilograms | Standard Deviation 7.889 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | MW 48, n=197, 212 | -3.20 Kilograms | Standard Deviation 7.951 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | MW 56, n=191, 206 | -2.95 Kilograms | Standard Deviation 8.427 |
| Placebo | Change From Baseline in Body Weight at the Indicated Time Points | Withdrawal from IP, n=106, 86 | -4.21 Kilograms | Standard Deviation 6.785 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Withdrawal from IP, n=106, 86 | -4.81 Kilograms | Standard Deviation 7.649 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Week 1, n=317, 343 | -0.04 Kilograms | Standard Deviation 2.263 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | MW 8, n=287, 287 | -5.67 Kilograms | Standard Deviation 5.326 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Week 2, n=314, 336 | -0.90 Kilograms | Standard Deviation 2.747 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | MW 40, n=208, 224 | -4.24 Kilograms | Standard Deviation 7.348 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Week 3, n=319, 328 | -1.46 Kilograms | Standard Deviation 2.889 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | MW 16, n=257, 275 | -5.64 Kilograms | Standard Deviation 6.12 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Week 4, n=316, 324 | -2.24 Kilograms | Standard Deviation 3.352 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | MW 56, n=191, 206 | -3.47 Kilograms | Standard Deviation 7.44 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Week 5, n=307, 309 | -3.30 Kilograms | Standard Deviation 3.803 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | MW 24, n=236, 252 | -5.15 Kilograms | Standard Deviation 6.723 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Week 6, n=314, 307 | -4.15 Kilograms | Standard Deviation 3.912 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | MW 48, n=197, 212 | -3.44 Kilograms | Standard Deviation 7.087 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | Week 7, n=290, 297 | -4.94 Kilograms | Standard Deviation 4.266 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | MW 32, n=220, 241 | -4.73 Kilograms | Standard Deviation 6.711 |
| Lapatinib 1500 mg | Change From Baseline in Body Weight at the Indicated Time Points | End of CRT, n=309, 311 | -5.36 Kilograms | Standard Deviation 4.406 |
Secondary
Change From Baseline in Heart Rate at the Indicated Time Points
Heart rate (HR) was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of chemoradiotherapy (CRT), Maintenance Week (MW) 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, Withdrawal from IP (up to Study Week 64)
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). 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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Week 1, n=312, 337 | -0.18 Beats per minute | Standard Deviation 10.414 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Week 2, n=303, 326 | -0.99 Beats per minute | Standard Deviation 10.91 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Week 3, n=306, 319 | -0.45 Beats per minute | Standard Deviation 10.701 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Week 4, n=307, 318 | -0.86 Beats per minute | Standard Deviation 11.116 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Week 5, n=298, 303 | -0.68 Beats per minute | Standard Deviation 11.673 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Week 6, n=306, 306 | -0.73 Beats per minute | Standard Deviation 11.933 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Week 7, n=279, 288 | 1.22 Beats per minute | Standard Deviation 11.491 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | End of CRT, n=300, 310 | 0.33 Beats per minute | Standard Deviation 12.362 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | MW 8, n=279, 277 | -0.30 Beats per minute | Standard Deviation 10.684 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | MW 16, n=256, 268 | -1.10 Beats per minute | Standard Deviation 11.238 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | MW 24, n=235, 251 | -0.98 Beats per minute | Standard Deviation 11.18 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | MW 32, n=213, 238 | -1.43 Beats per minute | Standard Deviation 11.934 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | MW 40, n=203, 222 | -2.72 Beats per minute | Standard Deviation 11.781 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | MW 48, n=200, 210 | -2.56 Beats per minute | Standard Deviation 12.158 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | MW 56, n=189, 204 | -3.08 Beats per minute | Standard Deviation 12.056 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Withdrawal from IP, n=99, 83 | 0.02 Beats per minute | Standard Deviation 12.719 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Withdrawal from IP, n=99, 83 | -0.69 Beats per minute | Standard Deviation 11.822 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 1, n=312, 337 | -0.84 Beats per minute | Standard Deviation 10.71 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | MW 8, n=279, 277 | 0.85 Beats per minute | Standard Deviation 10.632 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 2, n=303, 326 | -1.17 Beats per minute | Standard Deviation 10.258 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | MW 40, n=203, 222 | -0.96 Beats per minute | Standard Deviation 10.556 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 3, n=306, 319 | -1.24 Beats per minute | Standard Deviation 9.766 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | MW 16, n=256, 268 | -0.96 Beats per minute | Standard Deviation 11.129 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 4, n=307, 318 | -0.39 Beats per minute | Standard Deviation 11.645 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | MW 56, n=189, 204 | -1.16 Beats per minute | Standard Deviation 11.331 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 5, n=298, 303 | -0.39 Beats per minute | Standard Deviation 11.588 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | MW 24, n=235, 251 | -1.16 Beats per minute | Standard Deviation 9.793 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 6, n=306, 306 | -0.43 Beats per minute | Standard Deviation 10.947 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | MW 48, n=200, 210 | -0.93 Beats per minute | Standard Deviation 11.659 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 7, n=279, 288 | 0.40 Beats per minute | Standard Deviation 11.184 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | MW 32, n=213, 238 | -1.24 Beats per minute | Standard Deviation 10.549 |
| Lapatinib 1500 mg | Change From Baseline in Heart Rate at the Indicated Time Points | End of CRT, n=300, 310 | 0.54 Beats per minute | Standard Deviation 11.683 |
Secondary
Change From Baseline in Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale
Change from Baseline in quality of life status was assessed using the EQ-5D scale, a 5-item health status measure and a visual analog rating scale. Change from Baseline was analyzed using parametric analysis of covariance (with the Baseline value as a covariate). The EQ-5D is a generic measure of self-reported health outcomes that is applicable to a wide range of health conditions and treatments. The EQ-5D covers health status in 5 domains (3 questions each): mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each item is scored as follows: 1, no problems; 2, some moderate problems; 3, extreme problems. The possible EQ-5D index utility values range from 0.594 to 1, and the thermometer score ranges from 0 to 100. Higher scores represent better quality of life. Data were adjusted for participant-reported quality of life scores at Baseline.
Time frame: From randomization until the last follow-up/withdrawal visit (up to 62 study weeks)
Population: Safety Population. Only those participants who had a Baseline and post-Baseline score at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale | Utility score, n=172, 186 | 0.1 scores on a scale | Standard Error 0.01 |
| Placebo | Change From Baseline in Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale | Thermometer score, n=173, 197 | 5.5 scores on a scale | Standard Error 1.29 |
| Lapatinib 1500 mg | Change From Baseline in Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale | Utility score, n=172, 186 | 0.0 scores on a scale | Standard Error 0.01 |
| Lapatinib 1500 mg | Change From Baseline in Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale | Thermometer score, n=173, 197 | 3.2 scores on a scale | Standard Error 1.25 |
Secondary
Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire
Change from Baseline in quality of life status was assessed using the FACT-H&N questionnaire, which is designed to measure multidimensional quality of life in participants with head and neck cancer. Change from Baseline was analyzed using parametric analysis of covariance (with the Baseline value as a covariate). The FACT-H&N questionnaire contains 39 items (27 general questions and 12 head and neck cancer-specific items) covering 4 dimensions and 1 subscale: physical well-being, social/family well-being, emotional well-being, functional well-being, and a head and neck cancer subscale. Possible subscale scores range from 0 to 36. Higher scores represent better quality of life. Data were adjusted for participant-reported quality of life scores at Baseline.
Time frame: From randomization until the last follow-up/withdrawal visit (up to 62 study weeks)
Population: Safety Population. Only those participants who had a Baseline and post-Baseline score at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Social/Family Well-being, n=171, 189 | -0.3 scores on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Functional Well-being, n=168, 188 | 0.9 scores on a scale | Standard Error 0.39 |
| Placebo | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Emotional Well-being, n=169, 187 | 1.0 scores on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Head and Neck Cancer subscale, n=168, 189 | -1.2 scores on a scale | Standard Error 0.43 |
| Placebo | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Physical Well-being, n=171, 188 | 0.4 scores on a scale | Standard Error 0.33 |
| Lapatinib 1500 mg | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Head and Neck Cancer subscale, n=168, 189 | -1.7 scores on a scale | Standard Error 0.4 |
| Lapatinib 1500 mg | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Physical Well-being, n=171, 188 | -0.1 scores on a scale | Standard Error 0.31 |
| Lapatinib 1500 mg | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Social/Family Well-being, n=171, 189 | -1.7 scores on a scale | Standard Error 0.34 |
| Lapatinib 1500 mg | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Emotional Well-being, n=169, 187 | 0.0 scores on a scale | Standard Error 0.26 |
| Lapatinib 1500 mg | Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire | Functional Well-being, n=168, 188 | -0.4 scores on a scale | Standard Error 0.37 |
Secondary
Disease Specific Survival (DSS)
DSS is defined as the time from randomization until death due to head and neck cancer. Participants whose death was not related to the disease under study were treated as competing risks at the time death occured. Participants who were alive were censored at the time of their last visit.
Time frame: From randomization until death due to head and neck cancer (average of 131 study weeks)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Disease Specific Survival (DSS) | NA Months |
| Lapatinib 1500 mg | Disease Specific Survival (DSS) | NA Months |
Secondary
Extent of Exposure
Extent of exposure is defined as the duration of treatment administered during the study. The mean duration of treatment is calculated as the number of days between the start of treatment and the end of treatment inclusive (i.e., treatment stop date minus treatment start date + 1). Participants were counted in a treatment phase (monotherapy, chemoradiotherapy, and maintenance) if they had received any dose in that phase. Participants randomized to placebo who received \>=1 dose of lapatinib in error were included in the lapatinib arm.
Time frame: From randomization until end of 1year maintenance treatment (average of 63 study weeks)
Population: Safety Population (SP): all participants (par.) who were randomized and took \>=1 dose of study medication. Only par. available at the specified time points were analyzed (represented by n=X, X in the category titles). 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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Extent of Exposure | Monotherapy, n=332, 347 | 0.9 Weeks | Standard Deviation 0.32 |
| Placebo | Extent of Exposure | Chemoradiotherapy, n=327, 344 | 6.6 Weeks | Standard Deviation 1.29 |
| Placebo | Extent of Exposure | Maintenance, n=309, 321 | 41.5 Weeks | Standard Deviation 20 |
| Lapatinib 1500 mg | Extent of Exposure | Monotherapy, n=332, 347 | 0.9 Weeks | Standard Deviation 0.27 |
| Lapatinib 1500 mg | Extent of Exposure | Chemoradiotherapy, n=327, 344 | 6.5 Weeks | Standard Deviation 1.58 |
| Lapatinib 1500 mg | Extent of Exposure | Maintenance, n=309, 321 | 41.1 Weeks | Standard Deviation 21.03 |
Secondary
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points
A 12-lead ECG was recorded at Baseline, at the end of the CRT, at Maintenance Week 56, at withdrawal from IP, and at anytime post-baseline. Data are presented as clinically significant (CS) or not clinically significant (NCS) abnormal findings. The study investigator determined if an abnormal ECG finding was CS or NCS.
Time frame: Baseline (BL; within 8 weeks prior to randomization [Day 1]), End of CRT, Maintenance Week 56, Withdrawal from IP, and at any time Post-Baseline (up to Study Week 64)
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). 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) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Maintenance Week 56, Abnormal CS, n=166, 174 | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | End of CRT, Abnormal NCS, n=287, 292 | 76 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Withdrawal from IP, Abnormal NCS, n=70, 59 | 16 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | BL, Abnormal CS, n=334, 349 | 1 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Withdrawal from IP, Abnormal CS, n=70, 59 | 1 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | End of CRT, Abnormal CS, n=287, 292 | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Anytime post-baseline, Abnormal NCS, n=307, 312 | 94 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | BL, Abnormal NCS, n=334, 349 | 82 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Anytime post-baseline, Abnormal CS, n=307, 312 | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Maintenance Week 56, Abnormal NCS, n=166, 174 | 32 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Anytime post-baseline, Abnormal CS, n=307, 312 | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | BL, Abnormal NCS, n=334, 349 | 78 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | BL, Abnormal CS, n=334, 349 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | End of CRT, Abnormal NCS, n=287, 292 | 71 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | End of CRT, Abnormal CS, n=287, 292 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Maintenance Week 56, Abnormal CS, n=166, 174 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Withdrawal from IP, Abnormal NCS, n=70, 59 | 12 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Withdrawal from IP, Abnormal CS, n=70, 59 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Anytime post-baseline, Abnormal NCS, n=307, 312 | 88 Participants |
| Lapatinib 1500 mg | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points | Maintenance Week 56, Abnormal NCS, n=166, 174 | 32 Participants |
Secondary
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of non-serious AEs occurring at a frequency threshold of 5% and SAEs.
Time frame: From the first dose of lapatinib/placebo until 5 days after the last dose (average of 141 study weeks)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 328 Participants |
| Placebo | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 133 Participants |
| Lapatinib 1500 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 344 Participants |
| Lapatinib 1500 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 169 Participants |
Secondary
Number of Participants With a Second Primary Tumor
Participants who developed a second primary tumor at the time of the first recurrence or within 28 days of the first recurrence were measured. The criteria for a second primary tumor are as follows: a distinct lesion separated from the primary tumor site by \>2 centimeters of normal epithelium; or a new cancer with different histology; or any cancer, regardless of site, occurring \>=3 years after initial treatment. Participants with baseline disease were included in the denominator when calculating the percentage.
Time frame: From randomization until development of second primary tumor or within 28 days of first recurrence (average of 101 study weeks)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a Second Primary Tumor | 5 Participants |
| Lapatinib 1500 mg | Number of Participants With a Second Primary Tumor | 9 Participants |
Secondary
Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events
Late radiation morbidity event data are summarized as the number of participants with late radiation morbidity events per system organ class (SOC). Late radiation effects are defined as those that first occur 90 days or more after the initiation of radiation therapy.
Time frame: From 180 days after completion of radiation until the last follow-up/withdrawal visit (average of 64 study weeks)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Ear and labyrinth disorders | 2 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Gastrointestinal disorders | 25 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | General disorders | 8 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Skin and subcutaneous tissue disorders | 8 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Musculoskeletal and connective tissue | 13 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Respiratory, thoracic and mediastinal | 10 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Injury, poisoning and procedural | 13 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Nervous system disorders | 6 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Endocrine disorders | 4 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Infections and infestations | 3 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Investigations | 3 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Vascular disorders | 4 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Blood and lymphatic system disorders | 2 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Metabolism and nutrition disorders | 0 Participants |
| Placebo | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Neoplasm benign, malignant and unspecified | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Metabolism and nutrition disorders | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Endocrine disorders | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Gastrointestinal disorders | 23 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Blood and lymphatic system disorders | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | General disorders | 13 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Infections and infestations | 4 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Skin and subcutaneous tissue disorders | 13 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Ear and labyrinth disorders | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Musculoskeletal and connective tissue | 6 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Investigations | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Respiratory, thoracic and mediastinal | 7 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Neoplasm benign, malignant and unspecified | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Injury, poisoning and procedural | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Vascular disorders | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events | Nervous system disorders | 8 Participants |
Secondary
Number of Participants With the Indicated Biomarker Expression Status
Biomarkers (which influence clinical response) assessed from tumor tissues included P16, Human Papilloma virus (HPV), and Epidermal Growth Factor Receptor (EGFR)/Epidermal Growth Factor Receptor 1 (ErbB1). Biomarker expression is presented as positive, negative, or unknown. Participants in the ErbB1-positive category include those with results of positive or strongly positive.
Time frame: Baseline (BL; within 8 weeks prior to randomization [Day 1]) (up to Study Week 1)
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | Overall HPV, Negative | 284 Participants |
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | P16, Positive | 42 Participants |
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | P16, Negative | 282 Participants |
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | P16, Unknown | 18 Participants |
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | Overall HPV, Positive | 21 Participants |
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | Overall HPV, Unknown | 37 Participants |
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | ErbB1, Positive | 330 Participants |
| Placebo | Number of Participants With the Indicated Biomarker Expression Status | ErbB1, Negative | 12 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | ErbB1, Negative | 8 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | Overall HPV, Negative | 276 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | Overall HPV, Positive | 23 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | P16, Positive | 48 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | ErbB1, Positive | 338 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | P16, Negative | 271 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | Overall HPV, Unknown | 47 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Biomarker Expression Status | P16, Unknown | 27 Participants |
Secondary
Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit
Data are summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI CTC version 3.0) toxicity grades. Data are reported as the number of participants who had a grade 3 (G3) or grade 4 (G4) toxicity for the indicated chemistry parameters, where G3 indicates a severe toxicity and G4 indicates a life-threatening toxicity. Clinical chemistry parameters included: albumin, alkaline phosphatase (AP), alanine amino transferase (ALT), aspartate amino transeferase (AST), total bilirubin (TB), calcium, carbon dioxide content/bicarbonate (CO2/HCO3), creatinine, glucose, potassium, and sodium. The worst-case on-therapy visit includes any scheduled or unscheduled post-Baseline visit.
Time frame: From Baseline (within 8 weeks prior to randomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64)
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). 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) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | CO2/HCO3, Grade 4, n=187, 207 | 0 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TB, Grade 3, n=333, 348 | 3 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Creatinine, Grade 3, n=333, 348 | 3 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Albumin, Grade 4, n=330, 343 | 0 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Creatinine, Grade 4, n=333, 348 | 2 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TB, Grade 4, n=333, 348 | 0 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyperglycemia, Grade 3, n=332, 344 | 6 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | ALT, Grade 4, n=333, 348 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypergylcemia, Grade 4, n=332, 344 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypercalcemia , Grade 3, n=333, 348 | 3 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypoglycemia, Grade 3, n=332, 344 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AP, Grade 4, n=333, 347 | 0 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypogylcemia, Grade 4, n=332, 344 | 2 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypercalcemia , Grade 4, n=333, 348 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyperkalemia, Grade 3, n=333, 348 | 5 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AST, Grade 3, n=333, 347 | 5 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyperkalemia, Grade 4, n=333, 348 | 2 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypocalcemia , Grade 3, n=333, 348 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypokalemia, Grade 3, n=333, 348 | 17 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AP, Grade 3, n=333, 347 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypokalemia, Grade 4, n=333, 348 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypocalcemia , Grade 4, n=333, 348 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypernatremia, Grade 3, n=333, 348 | 0 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AST, Grade 4, n=333, 347 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypernatremia, Grade 4, n=333, 348 | 1 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | CO2/HCO3, Grade 3, n=187, 207 | 0 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyponatremia, Grade 3, n=333, 348 | 59 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | ALT, Grade 3, n=333, 348 | 9 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyponatremia, Grade 4, n=333, 348 | 11 Participants |
| Placebo | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Albumin, Grade 3, n=330, 343 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyponatremia, Grade 4, n=333, 348 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Albumin, Grade 3, n=330, 343 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Albumin, Grade 4, n=330, 343 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AP, Grade 3, n=333, 347 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AP, Grade 4, n=333, 347 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | ALT, Grade 3, n=333, 348 | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | ALT, Grade 4, n=333, 348 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AST, Grade 3, n=333, 347 | 5 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | AST, Grade 4, n=333, 347 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TB, Grade 3, n=333, 348 | 6 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TB, Grade 4, n=333, 348 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypercalcemia , Grade 3, n=333, 348 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypercalcemia , Grade 4, n=333, 348 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypocalcemia , Grade 3, n=333, 348 | 7 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypocalcemia , Grade 4, n=333, 348 | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | CO2/HCO3, Grade 3, n=187, 207 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | CO2/HCO3, Grade 4, n=187, 207 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Creatinine, Grade 3, n=333, 348 | 9 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Creatinine, Grade 4, n=333, 348 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyperglycemia, Grade 3, n=332, 344 | 8 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypergylcemia, Grade 4, n=332, 344 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypoglycemia, Grade 3, n=332, 344 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypogylcemia, Grade 4, n=332, 344 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyperkalemia, Grade 3, n=333, 348 | 8 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyperkalemia, Grade 4, n=333, 348 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypokalemia, Grade 3, n=333, 348 | 35 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypokalemia, Grade 4, n=333, 348 | 7 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypernatremia, Grade 3, n=333, 348 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hypernatremia, Grade 4, n=333, 348 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hyponatremia, Grade 3, n=333, 348 | 85 Participants |
Secondary
Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value
The Eastern Cooperative Oncology Group (ECOG) performance status scales and grades/criteria are used by doctors and researchers to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead.
Time frame: From Baseline (BL; within 8 weeks prior to randomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 0, n=317, 327 | 115 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 2, n=334, 348 | 19 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 3, n=334, 348 | 3 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 4-5, n=334, 348 | 1 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | BL, ECOG 0, n=336, 349 | 173 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | BL, ECOG 1, n=336, 349 | 161 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | BL, ECOG 2, n=336, 349 | 2 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 0, n=319, 342 | 160 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 1, n=319, 342 | 156 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 2, n=319, 342 | 3 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 3, n=319, 342 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 4-5, n=319, 342 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 0, n=313, 333 | 142 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 1, n=313, 333 | 166 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 2, n=313, 333 | 5 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 3, n=313, 333 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 4-5, n=313, 333 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 0, n=310, 329 | 138 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 1, n=310, 329 | 169 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 2, n=310, 329 | 3 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 3, n=310, 329 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 4-5, n=310, 329 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 1, n=334, 348 | 158 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 1, n=317, 327 | 191 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 2, n=317, 327 | 11 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 3, n=317, 327 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 4-5, n=317, 327 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 0, n=307, 312 | 100 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 1, n=307, 312 | 191 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 2, n=307, 312 | 16 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 3, n=307, 312 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 4-5, n=307, 312 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 0, n=312, 309 | 97 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 1, n=312, 309 | 187 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 2, n=312, 309 | 26 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 3, n=312, 309 | 2 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 4-5, n=312, 309 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 0, n=284, 295 | 83 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 1, n=284, 295 | 175 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 2, n=284, 295 | 23 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 3, n=284, 295 | 3 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 4-5, n=284, 295 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 0, n=307, 315 | 95 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 1, n=307, 315 | 184 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 2, n=307, 315 | 25 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 3, n=307, 315 | 3 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 4-5, n=307, 315 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 0, n=286, 290 | 132 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 1, n=286, 290 | 146 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 2, n=286, 290 | 7 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 3, n=286, 290 | 1 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 4-5, n=286, 290 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 0, n=260, 273 | 135 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 1, n=260, 273 | 124 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 2, n=260, 273 | 1 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 3, n=260, 273 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 4-5, n=260, 273 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 0, n=235, 251 | 122 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 1, n=235, 251 | 110 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 2, n=235, 251 | 3 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 3, n=235, 251 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 4-5, n=235, 251 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 0, n=218, 241 | 117 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 1, n=218, 241 | 99 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 2, n=218, 241 | 2 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 3, n=218, 241 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 4-5, n=218, 241 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 0, n=208, 227 | 118 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 1, n=208, 227 | 88 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 2, n=208, 227 | 2 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 3, n=208, 227 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 4-5, n=208, 227 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 0, n=205, 214 | 121 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 1, n=205, 214 | 81 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 2, n=205, 214 | 3 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 3, n=205, 214 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 4-5, n=205, 214 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 0, n=194, 211 | 107 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 1, n=194, 211 | 85 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 2, n=194, 211 | 2 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 3, n=194, 211 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 4-5, n=194, 211 | 0 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 0, n=109, 92 | 44 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 1, n=109, 92 | 50 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 2, n=109, 92 | 12 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 3, n=109, 92 | 2 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 4-5, n=109, 92 | 1 Participants |
| Placebo | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 0, n=334, 348 | 153 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 0, n=109, 92 | 38 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 1, n=334, 348 | 165 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 2, n=307, 315 | 45 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 2, n=334, 348 | 22 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 4-5, n=218, 241 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 3, n=334, 348 | 5 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 3, n=307, 315 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 4-5, n=334, 348 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 0, n=194, 211 | 111 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | BL, ECOG 0, n=336, 349 | 179 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 4-5, n=307, 315 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | BL, ECOG 1, n=336, 349 | 157 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 0, n=208, 227 | 130 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | BL, ECOG 2, n=336, 349 | 13 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 0, n=286, 290 | 128 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 0, n=319, 342 | 174 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 3, n=109, 92 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 1, n=319, 342 | 159 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 1, n=286, 290 | 153 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 2, n=319, 342 | 9 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 1, n=208, 227 | 94 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 3, n=319, 342 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 2, n=286, 290 | 9 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 1, ECOG 4-5, n=319, 342 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 1, n=194, 211 | 98 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 0, n=313, 333 | 149 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 3, n=286, 290 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 1, n=313, 333 | 168 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 2, n=208, 227 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 2, n=313, 333 | 16 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 8, ECOG 4-5, n=286, 290 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 3, n=313, 333 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 1, n=109, 92 | 40 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 2, ECOG 4-5, n=313, 333 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 0, n=260, 273 | 129 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 0, n=310, 329 | 131 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 3, n=208, 227 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 1, n=310, 329 | 183 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 1, n=260, 273 | 138 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 2, n=310, 329 | 15 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 2, n=194, 211 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 3, n=310, 329 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 2, n=260, 273 | 6 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 3, ECOG 4-5, n=310, 329 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 40, ECOG 4-5, n=208, 227 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 0, n=317, 327 | 111 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 3, n=260, 273 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 1, n=317, 327 | 194 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Last assessment on therapy, ECOG 0, n=334, 348 | 154 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 2, n=317, 327 | 21 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 16, ECOG 4-5, n=260, 273 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 3, n=317, 327 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 0, n=205, 214 | 111 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, ECOG 4-5, n=317, 327 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 0, n=235, 251 | 127 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 0, n=307, 312 | 95 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 3, n=194, 211 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 1, n=307, 312 | 183 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 1, n=235, 251 | 119 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 2, n=307, 312 | 30 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 1, n=205, 214 | 102 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 3, n=307, 312 | 4 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 2, n=235, 251 | 5 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 5, ECOG 4-5, n=307, 312 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 2, n=109, 92 | 11 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 0, n=312, 309 | 88 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 3, n=235, 251 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 1, n=312, 309 | 186 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 2, n=205, 214 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 2, n=312, 309 | 32 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 24, ECOG 4-5, n=235, 251 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 3, n=312, 309 | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 56, ECOG 4-5, n=194, 211 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 6, ECOG 4-5, n=312, 309 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 0, n=218, 241 | 123 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 0, n=284, 295 | 88 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 3, n=205, 214 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 1, n=284, 295 | 176 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 1, n=218, 241 | 115 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 2, n=284, 295 | 30 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal from IP, ECOG 4-5, n=109, 92 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 3, n=284, 295 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 2, n=218, 241 | 1 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 7, ECOG 4-5, n=284, 295 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 48, ECOG 4-5, n=205, 214 | 0 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 0, n=307, 315 | 84 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Maintenance week 32, ECOG 3, n=218, 241 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | End of CRT, ECOG 1, n=307, 315 | 186 Participants |
Secondary
Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit
Data are summarized using the NCI CTC version 3.0 toxicity grades. Data are reported as the number of participants who had a grade 3 (G3) or grade 4 (G4) toxicity for the indicated hematological parameters, where G3 indicates a severe toxicity and G4 indicates a life-threatening toxicity. The worst-case on-therapy visit includes any scheduled or unscheduled post-Baseline visit. Hematology parameter included: hemoglobin, total neutrophils (TN), platelet count (PC), and White Blood Cell (WBC) count.
Time frame: From Baseline (within 8 weeks prior torandomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64)
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). 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) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hemoglobin, Grade 3, n=333, 348 | 10 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hemoglobin, Grade 4, n=333, 348 | 0 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Lymphocytes, Grade 3, n=333, 348 | 203 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Lymphocytes, Grade 4, n=333, 348 | 34 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TN, Grade 3, n=333, 348 | 57 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TN, Grade 4, n=333, 348 | 6 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | PC, Grade 3, n=333, 348 | 0 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | PC, Grade 4, n=333, 348 | 2 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | WBC, Grade 3, n=333, 348 | 70 Participants |
| Placebo | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | WBC, Grade 4, n=333, 348 | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | PC, Grade 4, n=333, 348 | 2 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hemoglobin, Grade 3, n=333, 348 | 13 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TN, Grade 4, n=333, 348 | 13 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Hemoglobin, Grade 4, n=333, 348 | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | WBC, Grade 4, n=333, 348 | 6 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Lymphocytes, Grade 3, n=333, 348 | 208 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | PC, Grade 3, n=333, 348 | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | Lymphocytes, Grade 4, n=333, 348 | 48 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | WBC, Grade 3, n=333, 348 | 72 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit | TN, Grade 3, n=333, 348 | 47 Participants |
Secondary
Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline
LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart with each contraction. LVEF was assessed using echocardiogram (ECHO: a test of the action of the heart using ultrasound waves to produce a visual display, for the diagnosis or monitoring of heart disease ) and multigated acqusition scans (MUGA scan: a noninvasive diagnostic test used to evaluate the pumping function of the ventricles). Data from the ECHO and MUGA scans were combined, and the absolute change from Baseline (Abs) data are presented according to the following categories: No change or any increase, 0-\<10% decrease, 10-19% decrease, \>=20% decrease, \>=10% decrease and \>=the Lower Limit of Normal (LLN), \>=10% decrease and below LLN, \>=20% decrease and \>=LLN, or \>=20% decrease and below LLN. The relative percent change from Baseline (Rel) data are presented according to the following categories: \>=20% decrease and \>=LLN and \>=20% decrease and below LLN.
Time frame: From the end of the CRT until the last follow-up visit (average of 141 study weeks)
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, No change/any increase | 102 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >0 to <10% decrease | 138 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, 10 to 19% decrease | 65 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=20% decrease | 4 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=10% decrease and >=LLN | 62 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=10% decrease and below LLN | 7 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=20% decrease and >=LLN | 3 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=20% decrease and below LLN | 1 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Rel, >=20% decrease and >=LLN | 22 Participants |
| Placebo | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Rel, >=20% decrease and below LLN | 3 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=20% decrease and below LLN | 5 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, No change/any increase | 90 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=10% decrease and below LLN | 21 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >0 to <10% decrease | 131 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Rel, >=20% decrease and below LLN | 14 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, 10 to 19% decrease | 80 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=20% decrease and >=LLN | 5 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=20% decrease | 10 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Rel, >=20% decrease and >=LLN | 18 Participants |
| Lapatinib 1500 mg | Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline | Abs, >=10% decrease and >=LLN | 69 Participants |
Secondary
Overall Survival (OS)
OS is defined as the time from randomization until death due to any cause. For participants who did not die, the time to death was censored at the time of last visit/contact.
Time frame: From randomization until death due to any cause (average of 131 study weeks)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Survival (OS) | NA Months |
| Lapatinib 1500 mg | Overall Survival (OS) | NA Months |
Secondary
Time to Distant Relapse (TTDR)
TTDR is defined as the time from randomization until the first occurrence that distant relapse is documented. Distant relapse is defined as clear evidence of distant metastases (lung, bone, brain, etc.). Metastasis is defined as the spread of a cancer from one organ or part to another non-adjacent organ or part. All other events prior to a distant relapse were treated as competing risks at the time they occured. All other participants were treated as censored at the time of their last disease assessment. Participants with malignant disease at Baseline according to the independent review were censored at the time of randomization for the analysis of independently reviewed data.
Time frame: From randomization until the first documented occurrence that distant relapse is documented (average of 101 study weeks)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Distant Relapse (TTDR) | NA Months |
| Lapatinib 1500 mg | Time to Distant Relapse (TTDR) | NA Months |
Secondary
Time to Locoregional Recurrence (TTLR)
TTLR is defined as the time from randomization until the first occurrence that local and/or regional recurrence is documented or the date of censor. Local relapse is defined as recurrent cancer in the primary tumor bed not clearly attributable to a second primary neoplasm. Regional relapse is defined as recurrent cancer in the neck not clearly attributable to a second primary neoplasm. All other events prior to locoregional recurrence were treated as competing risks at the time they occured. All other participants were treated as censored at the time of their last disease assessment. Participants with malignant disease at Baseline according to the independent review were censored at the time of randomization for the analysis of independently reviewed data.
Time frame: From randomization until thefirst occurrence that local and/or regional recurrence is documented or the date of censor (average of 101 study weeks)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Locoregional Recurrence (TTLR) | NA Months |
| Lapatinib 1500 mg | Time to Locoregional Recurrence (TTLR) | NA Months |