A Study Of Lapatinib Versus Placebo Followed By Chemoradiation In Patients With Locally Advanced Head And Neck Cancer

A Randomized, Single Blinded, Placebo-controlled, Multi-centre, Phase II Study of Lapatinib in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00371566

Enrollment

107

Registered

2006-09-04

Start date

2006-03-31

Completion date

2007-12-31

Last updated

2010-04-06

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

Conditions

Squamous Cell Carcinoma of Head and Neck

Keywords

squamous cell carcinoma of head and neck, lapatinib, ErbB1/ErbB2 inhibitor, apoptosis

Brief summary

This is a study comparing the activity of lapatinib versus placebo followed by chemoradiation. This study is designed to explore the effects of lapatinib monotherapy on apoptosis/necrosis, in pre-treatment and post-treatment tumour tissue samples in subjects with locally advanced squamous cell carcinoma of head and neck.

Interventions

DRUGLapatinib oral tablets

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Willing and able to sign a written informed consent. * Histologically or cytologically confirmed diagnosis of SCCHN. * Stage III, IVA and IVB disease will be eligible, who are to receive chemoradiation therapy as primary treatment (total dose ≥ 65 Gy). Subjects with distant metastases (stage IVC) will be excluded. * Willing and able to have a tumour biopsy taken at screening and a second tumour biopsy taken during lapatinib/placebo administration. * Male or female ≥18 years of age. Criteria for female subjects or female partners of male subjects: Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; 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; implants of levonorgestrel; injectable progestogen; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only); or barrier methods, including diaphragm or condom with a spermicide. * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. * Subjects must have adequate haematological, renal and hepatic function. Calculated creatinine clearance ≥50 ml/min as determined by the method of Cockcroft and Gault \[Cockcroft, 1976\] or by the EDTA method. Absolute neutrophil count ≥1,500/μl, platelets ≥100,000/μl. Haemoglobin ≥9gm/dL (5mmol/L). Aspartate (AST) and alanine transaminase (ALT) less than three times the upper limit of the normal range (ULN). Total bilirubin ≤2.0 mg/dL. * Left ventricular ejection fraction (LVEF) within the institutional normal ranges as measured by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scans. * Able to swallow tablet whole or swallow a suspension of the tablet dissolved in water at study inclusion. If necessary, the suspension may be administered via percutaneous endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (JTube), or a nasogastric tube (NG or Dobhoff type tube). * Life expectancy of at least 6 months as judged by the investigator.

Exclusion criteria

* Subjects with paranasal sinuses, nasopharyngeal and nasal cavity tumours; * Subjects who have received prior systemic chemotherapy given with curative intent; * Subjects who received prior radiotherapy; * Prior or concurrent treatment with tyrosine kinase inhibitors; * Use of any investigational agent within 30 days or 5 half-lives, whichever is longer, preceding the first dose of lapatinib; * Concurrent use of CYP3A4 inducers or inhibitors; * Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; * 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 of head and neck that was successfully treated with surgery, photodynamics or laser, will be permitted; * Distant metastases, ie Stage IVC; * Females or males of child-bearing potential who are sexually active, if they do not agree to practice an effective method of contraception. (For example oral contraceptives, IUD or diaphragm plus spermicide); * Pregnant or lactating females (female patients of childbearing potential will undertake pregnancy testing at screening and during study completion/withdrawal visits); * Malabsorption syndrome, disease significantly affecting GI function, that could affect absorption of lapatinib; * History of allergic reactions to appropriate diuretics or antiemetics (e.g. 5-HT3 antagonists) to be administered with platinum-based chemotherapy; * The investigator considers the patient unfit for the study as a result of the medical interview, physical examinations, or screening investigations; * Subjects taking any prohibited medication (See Section 8.2) Other Eligibility Criteria Considerations: To assess any potential impact on subject eligibility with regard to safety, the investigator must refer to the following document(s) for detailed information regarding warnings,precautions, contraindications, adverse events, and other significant data pertaining to the investigational product(s) being used in this study: investigator's brochure IB and any IB supplements, and expedited investigator safety reports

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline of the Apoptotic Index During Treatment Phase	Baseline and Week 2	Apoptotic Index-TUNEL Assay is a method which counts a total of at least 1000 neoplastic nuclei(Cells with morphological changes defining cell death) subdivided in 10 fields chosen randomly at 400x magnification. A 'responder' was defined as having 20% cell death.

Secondary

Measure	Time frame	Description
Overall Radiological Response After Treatment Phase in mITT Population	Baseline and End of Treatment (Week 2 - 6)	Over all: Complete Response (CR)- absence of lesions. Partial Response (PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD) in other lesions with no new lesions or progressive disease (PD). Stable Disease (SD)-no PD or Response. Progressive Disease (PD)-PD or new lesions. Not Evaluable(NE)- no other definitions. Number of subjects included those who had a scan immediately post lapatanib/placebo monotherapy.
Overall Radiological Response After Follow-up Phase in mITT Population	Baseline and End of Follow-up (Week 19 - 25)	Over all: Complete Response(CR)-absence of lesions. Partial Response(PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD)in other lesions with no new lesions or progressive disease (PD). Stable Disease(SD)-no PD or Response. Progressive Disease(PD)-PD or new lesions. Not Evaluable(NE)- no other definitions. Number of subjects included those who were considered evaluable if they completed a full course of chemoradiotherapy and were able to provide a baseline and follow-up scan following the completion of chemoradiation.
Overall Radiological Response After Treatment Phase in ITT Population	Baseline and End of Treatment (Week 2 - 6)	Over all: Complete Response (CR)-absence of lesions. Partial Response (PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD) in other lesions with no new lesions or progressive disease (PD). Stable Disease (SD)-no PD or Response. Progressive Disease (PD)-PD or new lesions. Not Evaluable(NE)- no other definitions.
Overall Radiological Response After Follow-up Phase in ITT Population	Baseline and End of Follow-up (week 19 - 25)	Over all: Complete Response (CR) - absence of lesions. Partial Response (PR) - CR or PR of target lesions and incomplete response (IC) or stable disease (SD) in other lesions with no new lesions or progressive disease (PD). Stable Disease (SD)- no PD or Response. Progressive Disease (PD)- PD or new lesions. Not Evaluable(NE)- no other definitions.
Number of Circulating Tumor Cells at Baseline in mITT Population	Baseline	This measures the participants with Circulating Tumor Cells (CTC's)Pre-Treatment numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.
Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	End of Treatment (week 2 - 6)	This measures the participants with Circulating Tumor Cells (CTC's) after treatment numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.
Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	End of Chemoradiotherapy (week 10 - 13)	This measures the participants with Circulating Tumor Cells (CTC's) after chemoradiotherapy numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.
Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	Baseline and Week 2	Estrogen Receptor (ER) variants, ERB-B2 and ERB B-5 consist of the major proportion of ER expression both in normal and cancer tissues. The exact role of these markers are unknown. Acronyms defined: ICH (immunohistochemical) and FISH (fluorescence in situ hybridization).
Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Week 2	Tumor Suppressor p53 is welcomed and described as the guardian angel gene, it conserves stability by preventing genome mutation. Human Papillomavirus (HPV) biomarker is un-welcomed and is found to be an important precursor cancers of the head and neck. HPV biomarkers have the ability to bind to and inactivate the Tumor Suppressor p53 biomarker.
Summary of Adverse Events by Maximum Toxicity Grade Started During Treatment Phase	Week 1 through Week 6	Toxicity Grading scale 0=none, 1=transient symptom, 2=mild symptom that does not interfere with activities of daily living (ADL's) 3=mild but interfers with ADL's w/o hospitalization. 4=requires hopitalization 5=Death.
Summary of Adverse Events by Maximum Toxicity Grade (Grade 3 or Higher) Started During or After the Chemoradiotherapy Phase	Week 10 through 25	Toxicity Grading scale 0=none, 1= transient symptom, 2=mild symptom that does not interfere with activities of daily living (ADL's) 3=mild but interfers with ADL's w/o hospitalization. 4=requires hopitalization 5=Death.
Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Week 2 - 4	Position Emission Tomography (PET) scans 3-D images are read alongside CT or magnetic resonance imaging (MRI) scans, the combination gives both anatomic and metabolic information. CT = Computerized axial tomography; a type of x-ray for dense areas of the body. MRI = Magnetic Resonance Imaging which captures a picture using Magnets. Better = improvement in response, Worse = response was downgraded.
Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	weeks 19 - 25	Position Emission Tomography (PET) scans 3-D images are read alongside CT or magnetic resonance imaging (MRI) scans, the combination gives both anatomic and metabolic information. CT = Computerized axial tomography; a type of x-ray for dense areas of the body. MRI = Magnetic Resonance Imaging which captures a picture using Magnets. Better = improvement in response, Worse = response was downgraded.
Summary of Adverse Events Experienced by 15% or More Subjects in Either Treatment Group	Week 1 through 25	Definition of an adverse event is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Summary of Fatal/Serious Adverse Events During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or After the Chemoradiotherapy Phase. Definition of a serious adverse event is any untoward medicinal occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other.
Change From Baseline of Cell Proliferation Rate of the Ki-67 Proliferative Index in Tumour Biopsy Samples During Treatment Phase	Baseline and Week 2	The Ki-67 protein is expressed in all phases of the cell cycle except G0 (low level phase) and serves as a good marker for cell proliferation. Scoring is assessed by point counting 500 to 1000 cells, and is reported as percent positive cells. 20% positive cells to define positive (i.e. high risk)
Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or after Chemoradiotherapy Phase. Grade 3 are severe and undesirable Adverse Event (significant symptoms requiring hospitalization or invasive intervention; transfusion; elective interventional radiological procedure; therapeutic endoscopy or operation).
Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or after Chemoradiotherapy Phase. Grade 4 are life-threatening or disabling Adverse Event (complicated by acute, life-threatening metabolic or cardiovascular complications such as circulatory failure, hemorrhage, sepsis. Life-threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation).
Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or after Chemoradiotherapy Phase. Grade 5 are death related to Adverse Event.
Relative Change From Baseline of Ktrans Median (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Relative Change From Baseline of Kep Mean (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.
Relative Change From Baseline of Kep Perfused (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.
Relative Change From Baseline of Kep Whole (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.
Relative Change From Baseline of Ktrans Mean (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Relative Change From Baseline of Ktrans Perfused (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Relative Change From Baseline of Ktrans Whole (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Relative Change From Baseline of IAUC Median (90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of IAUC Mean (90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of Perfused IAUC (90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of Whole IAUC(90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of Kep Median (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.
Summary of Serious Adverse Events During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or After Chemoradiotherapy Phase. Definition of a serious adverse event is any untoward medicinal occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other.

Countries

France, Greece, India, Peru, Spain

Participant flow

Participants by arm

Arm	Count
Placebo Subjects who were given Placebo for 2 to 6 weeks followed by 4 weeks of standard treatment of radiotherapy (of more than or equal to 65 Gy) and concurrent platinum-based Chemotherapy (based on the intitutions standard of care)	36
Lapatinib Subjects who were given once daily dose of oral lapatinib 1500 mg for 2 -6 weeks, followed by 4 weeks of standard treatment of radiotherapy (of more than or equal to 65 Gy) and concurrent platinum-based chemotherapy (based on the institutions standard care).	71
Total	107

Withdrawals & dropouts

Period	Reason	FG000	FG001
Chemoradiation Phase	Death	2	0
Chemoradiation Phase	Non compliant	0	1
Chemoradiation Phase	Physician Decision	2	0
Chemoradiation Phase	Progressive Disease	1	1
Chemoradiation Phase	Withdrawal by Subject	0	1
Follow Up Phase	Death	0	5
Follow Up Phase	Disease progression	1	0
Follow Up Phase	Lost to Follow-up	1	0
Follow Up Phase	Physician Decision	1	1
Follow Up Phase	Withdrawal by Subject	0	1
Treatment Phase	Adverse Event	0	1
Treatment Phase	Protocol Violation	0	1
Treatment Phase	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Lapatinib	Total	Placebo
Age Continuous	57.7 years STANDARD_DEVIATION 11.01	57.1 years STANDARD_DEVIATION 10.83	56.2 years STANDARD_DEVIATION 10.47
Race/Ethnicity, Customized African American	0 participants	0 participants	0 participants
Race/Ethnicity, Customized American Indian or Alaska Native	11 participants	14 participants	3 participants
Race/Ethnicity, Customized Asian-Central and South Asian Heritage	19 participants	28 participants	9 participants
Race/Ethnicity, Customized Asian-Japanese East/South east Heritage	2 participants	4 participants	2 participants
Race/Ethnicity, Customized Asian-Mixed Heritage	0 participants	1 participants	1 participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 participants	0 participants	0 participants
Race/Ethnicity, Customized White	39 participants	60 participants	21 participants
Sex: Female, Male Female	16 Participants	20 Participants	4 Participants
Sex: Female, Male Male	55 Participants	87 Participants	32 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	36 / 36	69 / 69
serious Total, serious adverse events	14 / 36	14 / 69

Outcome results

Primary

Change From Baseline of the Apoptotic Index During Treatment Phase

Apoptotic Index-TUNEL Assay is a method which counts a total of at least 1000 neoplastic nuclei(Cells with morphological changes defining cell death) subdivided in 10 fields chosen randomly at 400x magnification. A 'responder' was defined as having 20% cell death.

Time frame: Baseline and Week 2

Population: The Intent-to-treat (ITT) population comprised of all subjects who were randomised to study treatment, regardless of whether they actually received study medication.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Change From Baseline of the Apoptotic Index During Treatment Phase	6.2 Percentage of positive cells	Standard Deviation 12.1
Lapatinib	Change From Baseline of the Apoptotic Index During Treatment Phase	4.2 Percentage of positive cells	Standard Deviation 5.53

Comparison: The study was designed to provide evidence to support the null hypothesis: Delta equals 0% or reject it in favor of the two sided alternative hypothesis: Delta does not equal 0%, where Delta was the difference in the true response rate for the two treatment groups.p-value: 0.39495% CI: [-5.5, 2.19]ANCOVA

Secondary

Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase

Events which started during or after Chemoradiotherapy Phase. Grade 4 are life-threatening or disabling Adverse Event (complicated by acute, life-threatening metabolic or cardiovascular complications such as circulatory failure, hemorrhage, sepsis. Life-threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation).

Time frame: Week 10 through 25

Population: Safety population consisted of all randomized subjects who took at least one dose of study medication. This population was based on the actual treatment received, if different to the randomized treatment allocation.

Arm	Measure	Group	Value (NUMBER)
Placebo	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Dyspnoea	0 Participants
Placebo	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Neutropenia	1 Participants
Placebo	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Hypernatraemia	0 Participants
Placebo	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Anaemia	0 Participants
Placebo	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Mucosal inflammation	0 Participants
Placebo	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Skin reaction	0 Participants
Lapatinib	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Mucosal inflammation	2 Participants
Lapatinib	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Anaemia	2 Participants
Lapatinib	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Neutropenia	0 Participants
Lapatinib	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Skin reaction	1 Participants
Lapatinib	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Hypernatraemia	1 Participants
Lapatinib	Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Dyspnoea	1 Participants

Secondary

Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase

Events which started during or after Chemoradiotherapy Phase. Grade 3 are severe and undesirable Adverse Event (significant symptoms requiring hospitalization or invasive intervention; transfusion; elective interventional radiological procedure; therapeutic endoscopy or operation).

Time frame: Week 10 through 25

Arm	Measure	Group	Value (NUMBER)
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Respiratory failure	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Radiation mucositis	2 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Skin reaction	3 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Weight decreased	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Skin ulcer	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Pain	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Haemoglobin decreased	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Lymphopenia	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Dysphagia	3 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Leucopenia	2 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Asthenia	2 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Aspartate aminotransferase increased	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Dysphonia	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Trismus	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Soft tissue inflammation	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Diplopia	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Bipolar disorder	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Odynophagia	2 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Localised oedema	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Neutropenia	3 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Vomiting	3 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Respiratory tract infection	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	General physical health deterioration	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Sepsis	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Peripheral embolism	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Hyponatraemia	2 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Rash	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Ketoacidosis	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Post procedural haemorrhage	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Nausea	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Blood creatinine increased	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Radiation skin injury	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Haematocrit decreased	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Renal failure	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Back pain	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Constipation	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Deep vein thrombosis	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Stomatitis	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Dry mouth	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Mucosal inflammation	9 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Dry mouth	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Mucosal inflammation	24 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Skin reaction	6 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Neutropenia	4 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Dysphagia	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Constipation	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Skin ulcer	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Bipolar disorder	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Peripheral embolism	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Vomiting	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Respiratory failure	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Haematocrit decreased	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Lymphopenia	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Asthenia	3 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Soft tissue inflammation	2 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Odynophagia	2 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	General physical health deterioration	2 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Rash	2 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Radiation skin injury	2 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Nausea	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Stomatitis	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Radiation mucositis	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Weight decreased	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Pain	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Ketoacidosis	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Dysphonia	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Leucopenia	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Aspartate aminotransferase increased	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Trismus	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Diplopia	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Renal failure	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Localised oedema	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Respiratory tract infection	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Sepsis	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Hyponatraemia	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Post procedural haemorrhage	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Blood creatinine increased	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Haemoglobin decreased	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Back pain	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Deep vein thrombosis	0 Participants

Secondary

Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase

Events which started during or after Chemoradiotherapy Phase. Grade 5 are death related to Adverse Event.

Time frame: Week 10 through 25

Arm	Measure	Group	Value (NUMBER)
Placebo	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Intestinal perforation	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Sudden death	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Ventricular fibrillation	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Cardio-respiratory arrest	0 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Staphyloccocal sepsis	1 Participants
Placebo	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Respiratory tract infection	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Staphyloccocal sepsis	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Ventricular fibrillation	0 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Intestinal perforation	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Cardio-respiratory arrest	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Sudden death	1 Participants
Lapatinib	Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Respiratory tract infection	1 Participants

Secondary

Change From Baseline of Cell Proliferation Rate of the Ki-67 Proliferative Index in Tumour Biopsy Samples During Treatment Phase

The Ki-67 protein is expressed in all phases of the cell cycle except G0 (low level phase) and serves as a good marker for cell proliferation. Scoring is assessed by point counting 500 to 1000 cells, and is reported as percent positive cells. 20% positive cells to define positive (i.e. high risk)

Time frame: Baseline and Week 2

Population: The mITT (modified Intent-to-Treat) population consisted of all subjects who were randomised to study treatment, did not miss lapatinib/placebo treatment for more than 7 consecutive days and had provided sufficient tumor biopsy sample for the primary endpoint analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Change From Baseline of Cell Proliferation Rate of the Ki-67 Proliferative Index in Tumour Biopsy Samples During Treatment Phase	-1.2 Percent of positive cells	Standard Deviation 7.9
Lapatinib	Change From Baseline of Cell Proliferation Rate of the Ki-67 Proliferative Index in Tumour Biopsy Samples During Treatment Phase	-5.6 Percent of positive cells	Standard Deviation 12.53

Secondary

Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information

Position Emission Tomography (PET) scans 3-D images are read alongside CT or magnetic resonance imaging (MRI) scans, the combination gives both anatomic and metabolic information. CT = Computerized axial tomography; a type of x-ray for dense areas of the body. MRI = Magnetic Resonance Imaging which captures a picture using Magnets. Better = improvement in response, Worse = response was downgraded.

Time frame: weeks 19 - 25

Population: The mITT population consisted of all subjects who were randomised to study treatment, did not miss lapatinib/placebo treatment for more than 7 consecutive days and had provided sufficient tumour biopsy sample for the primary endpoint analysis.

Arm	Measure	Group	Value (NUMBER)
Placebo	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Better	0 Participants
Placebo	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Same	11 Participants
Placebo	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Worse	1 Participants
Placebo	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Any Unknown	0 Participants
Placebo	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Not Evaluable	0 Participants
Placebo	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Missing	1 Participants
Lapatinib	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Not Evaluable	0 Participants
Lapatinib	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Better	2 Participants
Lapatinib	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Any Unknown	0 Participants
Lapatinib	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Same	10 Participants
Lapatinib	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Missing	0 Participants
Lapatinib	Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	Worse	5 Participants

Secondary

Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information

Time frame: Week 2 - 4

Arm	Measure	Group	Value (NUMBER)
Placebo	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Better	2 Participants
Placebo	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Same	8 Participants
Placebo	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Worse	0 Participants
Placebo	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Any Unknown	0 Participants
Placebo	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Missing	1 Participants
Placebo	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Not Evaluable	0 Participants
Lapatinib	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Missing	0 Participants
Lapatinib	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Better	3 Participants
Lapatinib	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Any Unknown	0 Participants
Lapatinib	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Same	6 Participants
Lapatinib	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Not Evaluable	2 Participants
Lapatinib	Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Worse	3 Participants

Secondary

Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase

Estrogen Receptor (ER) variants, ERB-B2 and ERB B-5 consist of the major proportion of ER expression both in normal and cancer tissues. The exact role of these markers are unknown. Acronyms defined: ICH (immunohistochemical) and FISH (fluorescence in situ hybridization).

Time frame: Baseline and Week 2

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Treatment 2+ expressed	11 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 0 expressed	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 3+ expressed	3 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Treatment 3+ expressed	2 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 3+ expressed	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 0 expressed	2 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 0 expressed	2 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 1+ expressed	2 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 1+ expressed	1 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 2+ expressed	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 2+ expressed	1 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 3+ expressed	23 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 3+ expressed	23 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Baseline Amplified	8 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Treatment Amplified	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Baseline Non Amplified	19 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Treatment Non Amplified	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 0 expressed	19 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 0 expressed	15 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 1+ expressed	11 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 2+ expressed	2 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 2+ expressed	1 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 3+ expressed	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 3+ expressed	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Baseline Amplified	2 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Treatment Amplified	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Baseline Non Amplified	25 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Treatment Non Amplified	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 1+ expressed	13 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Treatment 1+ expressed	14 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 2+ expressed	11 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 1+ expressed	6 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 0 expressed	13 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 0 expressed	13 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 1+ expressed	12 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 1+ expressed	12 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 2+ expressed	1 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 2+ expressed	1 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 3+ expressed	0 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline - Missing expression	1 Participants
Placebo	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment Missing expression	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Treatment 3+ expressed	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 1+ expressed	13 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Treatment Non Amplified	2 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 2+ expressed	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Treatment 2+ expressed	15 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment Missing expression	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 3+ expressed	5 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 3+ expressed	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 0 expressed	25 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 3+ expressed	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 0 expressed	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 2+ expressed	4 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 0 expressed	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Baseline Amplified	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 1+ expressed	2 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 0 expressed	24 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 1+ expressed	4 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Treatment Amplified	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 2+ expressed	10 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 3+ expressed	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 2+ expressed	5 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by FISH-Baseline Non Amplified	54 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Baseline 3+ expressed	45 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 1+ expressed	30 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by IHC-Treatment 3+ expressed	48 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 0 expressed	3 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Baseline Amplified	17 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline - Missing expression	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Treatment Amplified	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 1+ expressed	31 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Baseline Non Amplified	40 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 1+ expressed	29 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB1 by FISH-Treatment Non Amplified	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Treatment 1+ expressed	38 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 0 expressed	42 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Treatment 3+ expressed	0 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 0 expressed	26 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB1 by IHC-Baseline 2+ expressed	18 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Treatment 1+ expressed	29 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	pErbB2 by IHC-Baseline 2+ expressed	1 Participants
Lapatinib	Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	ErbB2 by IHC-Baseline 2+ expressed	1 Participants

Secondary

Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase

Tumor Suppressor p53 is welcomed and described as the guardian angel gene, it conserves stability by preventing genome mutation. Human Papillomavirus (HPV) biomarker is un-welcomed and is found to be an important precursor cancers of the head and neck. HPV biomarkers have the ability to bind to and inactivate the Tumor Suppressor p53 biomarker.

Time frame: Week 2

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 1+ expression	5 Participants
Placebo	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 3+ expression	14 Participants
Placebo	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - missing expression	0 Participants
Placebo	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	HPV - Negative	36 Participants
Placebo	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 0 expression	14 Participants
Placebo	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	HPV - Positive	0 Participants
Placebo	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 2+ expression	3 Participants
Lapatinib	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	HPV - Positive	5 Participants
Lapatinib	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 2+ expression	11 Participants
Lapatinib	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 3+ expression	19 Participants
Lapatinib	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 0 expression	25 Participants
Lapatinib	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - missing expression	0 Participants
Lapatinib	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	HPV - Negative	64 Participants
Lapatinib	Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Tumor Protein 53 - 1+ expression	14 Participants

Secondary

Number of Circulating Tumor Cells at Baseline in mITT Population

This measures the participants with Circulating Tumor Cells (CTC's)Pre-Treatment numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.

Time frame: Baseline

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Circulating Tumor Cells at Baseline in mITT Population	No result	2 Participants
Placebo	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 2	1 Participants
Placebo	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 3	0 Participants
Placebo	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 0	7 Participants
Placebo	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's ≥4	0 Participants
Placebo	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 1	2 Participants
Lapatinib	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's ≥4	1 Participants
Lapatinib	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 1	1 Participants
Lapatinib	Number of Circulating Tumor Cells at Baseline in mITT Population	No result	2 Participants
Lapatinib	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 0	18 Participants
Lapatinib	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 2	0 Participants
Lapatinib	Number of Circulating Tumor Cells at Baseline in mITT Population	Number of CTC's 3	0 Participants

Secondary

Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population

This measures the participants with Circulating Tumor Cells (CTC's) after chemoradiotherapy numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.

Time frame: End of Chemoradiotherapy (week 10 - 13)

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's >=4	0 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 2	0 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 1	0 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 3	1 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	No result	0 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 0	4 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	No result	0 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 3	0 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's >=4	0 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 0	2 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 1	0 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	Number of CTC's 2	0 Participants

Secondary

Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population

This measures the participants with Circulating Tumor Cells (CTC's) after treatment numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.

Time frame: End of Treatment (week 2 - 6)

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 0	12 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 2	0 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	No result	1 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 3	0 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 1	0 Participants
Placebo	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's >=4	0 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 1	3 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	No result	0 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 0	13 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's >=4	2 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 2	1 Participants
Lapatinib	Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	Number of CTC's 3	0 Participants

Secondary

Overall Radiological Response After Follow-up Phase in ITT Population

Time frame: Baseline and End of Follow-up (week 19 - 25)

Population: The Intent-to-treat (ITT) population comprised of all subjects who were randomised to study treatment, regardless of whether they actually received study medication.

Arm	Measure	Group	Value (NUMBER)
Placebo	Overall Radiological Response After Follow-up Phase in ITT Population	Complete Response	2 Participants
Placebo	Overall Radiological Response After Follow-up Phase in ITT Population	Partial Response	17 Participants
Placebo	Overall Radiological Response After Follow-up Phase in ITT Population	Stable Disease	2 Participants
Placebo	Overall Radiological Response After Follow-up Phase in ITT Population	Progressive Disease	9 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in ITT Population	Progressive Disease	4 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in ITT Population	Complete Response	16 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in ITT Population	Stable Disease	4 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in ITT Population	Partial Response	34 Participants

Secondary

Overall Radiological Response After Follow-up Phase in mITT Population

Over all: Complete Response(CR)-absence of lesions. Partial Response(PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD)in other lesions with no new lesions or progressive disease (PD). Stable Disease(SD)-no PD or Response. Progressive Disease(PD)-PD or new lesions. Not Evaluable(NE)- no other definitions. Number of subjects included those who were considered evaluable if they completed a full course of chemoradiotherapy and were able to provide a baseline and follow-up scan following the completion of chemoradiation.

Time frame: Baseline and End of Follow-up (Week 19 - 25)

Arm	Measure	Group	Value (NUMBER)
Placebo	Overall Radiological Response After Follow-up Phase in mITT Population	Progressive Disease	6 Participants
Placebo	Overall Radiological Response After Follow-up Phase in mITT Population	Stable Disease	2 Participants
Placebo	Overall Radiological Response After Follow-up Phase in mITT Population	Partial Response	13 Participants
Placebo	Overall Radiological Response After Follow-up Phase in mITT Population	Complete Response	2 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in mITT Population	Progressive Disease	4 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in mITT Population	Complete Response	11 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in mITT Population	Partial Response	29 Participants
Lapatinib	Overall Radiological Response After Follow-up Phase in mITT Population	Stable Disease	3 Participants

Secondary

Overall Radiological Response After Treatment Phase in ITT Population

Time frame: Baseline and End of Treatment (Week 2 - 6)

Population: The Intent-to-treat (ITT) population comprised of all subjects who were randomised to study treatment, regardless of whether they actually received study medication.

Arm	Measure	Group	Value (NUMBER)
Placebo	Overall Radiological Response After Treatment Phase in ITT Population	Stable Disease	12 Participants
Placebo	Overall Radiological Response After Treatment Phase in ITT Population	Non-Evaluable	0 Participants
Placebo	Overall Radiological Response After Treatment Phase in ITT Population	Complete Response	0 Participants
Placebo	Overall Radiological Response After Treatment Phase in ITT Population	Progressive Disease	4 Participants
Placebo	Overall Radiological Response After Treatment Phase in ITT Population	Partial Response	0 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in ITT Population	Progressive Disease	0 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in ITT Population	Non-Evaluable	5 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in ITT Population	Stable Disease	15 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in ITT Population	Partial Response	3 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in ITT Population	Complete Response	1 Participants

Secondary

Overall Radiological Response After Treatment Phase in mITT Population

Over all: Complete Response (CR)- absence of lesions. Partial Response (PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD) in other lesions with no new lesions or progressive disease (PD). Stable Disease (SD)-no PD or Response. Progressive Disease (PD)-PD or new lesions. Not Evaluable(NE)- no other definitions. Number of subjects included those who had a scan immediately post lapatanib/placebo monotherapy.

Time frame: Baseline and End of Treatment (Week 2 - 6)

Arm	Measure	Group	Value (NUMBER)
Placebo	Overall Radiological Response After Treatment Phase in mITT Population	Partial Response	0 Participants
Placebo	Overall Radiological Response After Treatment Phase in mITT Population	Progressive Disease	2 Participants
Placebo	Overall Radiological Response After Treatment Phase in mITT Population	Stable Disease	10 Participants
Placebo	Overall Radiological Response After Treatment Phase in mITT Population	Non-Evaluable	0 Participants
Placebo	Overall Radiological Response After Treatment Phase in mITT Population	Complete Response	0 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in mITT Population	Non-Evaluable	4 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in mITT Population	Complete Response	1 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in mITT Population	Partial Response	3 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in mITT Population	Stable Disease	12 Participants
Lapatinib	Overall Radiological Response After Treatment Phase in mITT Population	Progressive Disease	0 Participants

Secondary

Relative Change From Baseline of IAUC Mean (90) After 2 - 4 Weeks of Treatment

Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.