Study Of Adjuvant Lapatinib In High-Risk Head And Neck Cancer Subjects After Surgery

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00424255
• Collaborator: (none)
• Enrollment: 688
• Locations: 117
• Arms: 2
• Duration (Months): 83
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms, Head and Neck	Drug: Lapatinib; Radiation: Chemoradiation; Other: Placebo	Phase 3

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)

Study Design

• Study Type: Interventional
• Actual Enrollment: 688 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lapatinib+Chemoradiation Adjuvant concurrent chemoradiotherapy plus lapatinib 1500 mg once daily for 6 to 7 weeks, followed by lapatinib 1500 mg once daily for one year. Chemoradiotherapy=total dose of 66Gy over 6-7 weeks plus cisplatin 100mg/m2 on days 1,2 and 43 of the course of radiotherapy. Lapatinib is also given at 1500 mg once daily for 3-7 days prior to the start of chemoradiotherapy.	Drug: Lapatinib; Dual ErbB1/2 inhibitor
Placebo Comparator: Placebo+Chemoradiation Adjuvant concurrent chemoradiotherapy plus placebo once daily for 6 to 7 weeks, followed by placebo once daily for one year. Chemoradiotherapy = total dose of 66Gy over 6-7 weeks plus cisplatin 100mg/m2 on days 1,2 and 43 of the course of treatment. Placebo is also given once daily for 3-7 days prior to the start of chemoradiotherapy.	Radiation: Chemoradiation; Radiation plus platinum based chemotherapy; Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Springfield	Illinois	United States	62794
2	GSK Investigational Site	Saint Louis	Missouri	United States	63110
3	GSK Investigational Site	New York	New York	United States	10003
4	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599-7600
5	GSK Investigational Site	Lubbock	Texas	United States	79415
6	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1185AAT
7	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2000KZE
8	GSK Investigational Site	Quilmes		Argentina	1878
9	GSK Investigational Site	Santa Fe		Argentina	3000
10	GSK Investigational Site	Innsbruck		Austria	A-6020
11	GSK Investigational Site	Rankweil		Austria	A-6830
12	GSK Investigational Site	Salzburg		Austria	A-5020
13	GSK Investigational Site	Vienna		Austria	1130
14	GSK Investigational Site	Vienna		Austria	A-1090
15	GSK Investigational Site	Edmonton	Alberta	Canada	T6G 1Z2
16	GSK Investigational Site	Halifax	Nova Scotia	Canada	B3H 1V7
17	GSK Investigational Site	London	Ontario	Canada	N6A 4L6
18	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 5N4
19	GSK Investigational Site	Quebec		Canada	G1R 2J6
20	GSK Investigational Site	Guangzhou	Guangdong	China	510060
21	GSK Investigational Site	Wuhan	Hubei	China	430030
22	GSK Investigational Site	Beijing		China	100021
23	GSK Investigational Site	Beijing		China	100036
24	GSK Investigational Site	Fuzhou		China	350014
25	GSK Investigational Site	Shanghai		China	200032
26	GSK Investigational Site	Tianjin		China	300060
27	GSK Investigational Site	Zagreb		Croatia	10 000
28	GSK Investigational Site	Zagreb		Croatia	10000
29	GSK Investigational Site	Brno		Czech Republic	65691
30	GSK Investigational Site	Olomouc		Czech Republic	775 20
31	GSK Investigational Site	Ostrava - Poruba		Czech Republic	708 52
32	GSK Investigational Site	Praha 8		Czech Republic	180 00
33	GSK Investigational Site	Tallinn		Estonia	13419
34	GSK Investigational Site	Angers Cedex 09		France	49933
35	GSK Investigational Site	Annecy		France	74000
36	GSK Investigational Site	Caen		France	14033
37	GSK Investigational Site	Colmar		France	68024
38	GSK Investigational Site	Ferolles-Attilly		France	77150
39	GSK Investigational Site	La Roche sur Yon		France	85025
40	GSK Investigational Site	Lille		France	59000
41	GSK Investigational Site	Lyon		France	69008
42	GSK Investigational Site	Montpellier Cedex 5		France	34298
43	GSK Investigational Site	Paris		France	75970
44	GSK Investigational Site	Reims		France	51100
45	GSK Investigational Site	Saint Cloud		France	92210
46	GSK Investigational Site	Strasbourg		France	67085
47	GSK Investigational Site	Toulouse		France	31052
48	GSK Investigational Site	Villejuif Cedex		France	94805
49	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
50	GSK Investigational Site	Karlsruhe	Baden-Wuerttemberg	Germany	76135
51	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
52	GSK Investigational Site	Halle	Sachsen-Anhalt	Germany	06097
53	GSK Investigational Site	Dresden	Sachsen	Germany	01067
54	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
55	GSK Investigational Site	Athens		Greece	142 33
56	GSK Investigational Site	Athens		Greece	15125
57	GSK Investigational Site	Haidari, Athens		Greece	12462
58	GSK Investigational Site	Neo Faliro		Greece	18547
59	GSK Investigational Site	Peiraius		Greece	185 37
60	GSK Investigational Site	Hong Kong		Hong Kong
61	GSK Investigational Site	Kowloon		Hong Kong
62	GSK Investigational Site	Budapest		Hungary	1115
63	GSK Investigational Site	Budapest		Hungary	1122
64	GSK Investigational Site	Szombathely		Hungary	9700
65	GSK Investigational Site	Kochi		India	682026
66	GSK Investigational Site	Mumbai		India	400 016
67	GSK Investigational Site	Mumbai		India	400012
68	GSK Investigational Site	Pune		India	411001
69	GSK Investigational Site	Trivandrum		India	695011
70	GSK Investigational Site	Galway		Ireland
71	GSK Investigational Site	Rathgar, Dublin		Ireland	6
72	GSK Investigational Site	Napoli	Campania	Italy	80131
73	GSK Investigational Site	Genova	Liguria	Italy	16132
74	GSK Investigational Site	Milano	Lombardia	Italy	20132
75	GSK Investigational Site	Milano	Lombardia	Italy	20141
76	GSK Investigational Site	Pavia	Lombardia	Italy	27100
77	GSK Investigational Site	Venezia	Veneto	Italy	30122
78	GSK Investigational Site	Manila		Philippines	1000
79	GSK Investigational Site	Moscow		Russian Federation	115478
80	GSK Investigational Site	Moscow		Russian Federation	129128
81	GSK Investigational Site	St. Petersburg		Russian Federation	198255
82	GSK Investigational Site	Ufa,		Russian Federation	450054
83	GSK Investigational Site	Bratislava		Slovakia	812 50
84	GSK Investigational Site	Kosice		Slovakia	041 91
85	GSK Investigational Site	Barcelona		Spain	08025
86	GSK Investigational Site	Barcelona		Spain	08035
87	GSK Investigational Site	Cordoba		Spain	14004
88	GSK Investigational Site	Gerona		Spain	17007
89	GSK Investigational Site	Granada		Spain	18014
90	GSK Investigational Site	Huesca		Spain	22300
91	GSK Investigational Site	Lerida		Spain	25198
92	GSK Investigational Site	Madrid		Spain	28033
93	GSK Investigational Site	Madrid		Spain	28034
94	GSK Investigational Site	Madrid		Spain	28040
95	GSK Investigational Site	Madrid		Spain	28041
96	GSK Investigational Site	Madrid		Spain	28046
97	GSK Investigational Site	Murcia		Spain	30008
98	GSK Investigational Site	Orense		Spain	32005
99	GSK Investigational Site	Santander		Spain	39008
100	GSK Investigational Site	Santiago de Compostela		Spain	15706
101	GSK Investigational Site	Sevilla		Spain	41009
102	GSK Investigational Site	Valencia		Spain	46009
103	GSK Investigational Site	Zaragoza		Spain	50009
104	GSK Investigational Site	Bangkok		Thailand	10330
105	GSK Investigational Site	Bangkok		Thailand	10400
106	GSK Investigational Site	Chiangmai		Thailand	50200
107	GSK Investigational Site	Cambridge	Cambridgeshire	United Kingdom	CB2 2QQ
108	GSK Investigational Site	Northwood	Middlesex	United Kingdom	HA6 2RN
109	GSK Investigational Site	Edinburgh	Midlothian	United Kingdom	EH4 2XU
110	GSK Investigational Site	Brighton	Sussex East	United Kingdom	BN2 5BE
111	GSK Investigational Site	Guildford		United Kingdom	GU2 7XX
112	GSK Investigational Site	London		United Kingdom	NW1 2PG
113	GSK Investigational Site	London		United Kingdom	SE1 7EH
114	GSK Investigational Site	London		United Kingdom	SW3 6JJ
115	GSK Investigational Site	Newcastle upon Tyne		United Kingdom	NE7 7DN
116	GSK Investigational Site	Sheffield		United Kingdom	S10 2SJ
117	GSK Investigational Site	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00424255
• Other Study ID Numbers: EGF102988
• First Posted: Jan 19, 2007
• Last Update Posted: Jul 18, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by GlaxoSmithKline: Cancer of the Head and Neck; Neck cancer; Adjuvant; Head and neck cancer; High-risk head and neck cancer; Post-surgery; Head cancer
• Additional relevant MeSH terms: Head and Neck Neoplasms; Lapatinib

Study Results

Participant Flow

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	342	346
COMPLETED	0	0
NOT COMPLETED	342	346

Baseline Characteristics

Arm/Group Title	Placebo	Lapatinib 1500 mg	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	342	346	688
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.7 (9.85)	53.8 (8.38)	53.8 (9.14)
Sex: Female, Male (Count of Participants)
Female	55 16.1%	60 17.3%	115 16.7%
Male	287 83.9%	286 82.7%	573 83.3%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	1 0.3%	0 0%	1 0.1%
Asian - Central/South Asian Heritage	61 17.8%	53 15.3%	114 16.6%
Asian - East Asian Heritage	41 12%	47 13.6%	88 12.8%
Asian - South East Asian Heritage	19 5.6%	23 6.6%	42 6.1%
Asian - Mixed Race	0 0%	1 0.3%	1 0.1%
White - Arabic/North African Heritage	1 0.3%	3 0.9%	4 0.6%
White - White/Caucasian/European Heritage	219 64%	219 63.3%	438 63.7%

Outcome Measures

1. Primary Outcome

Title	Disease Free Survival (DFS)
Description	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)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who were randomized to study treatment, irrespective of whether they actually received study medication

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	342	346
Median (95% Confidence Interval) [Months]	NA	53.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lapatinib 1500 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2251
	Comments	The one-sided p-value is unstratified as there are too few events per stratum to perform a stratified test.
	Method	Non-stratified log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lapatinib 1500 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4502
	Comments	The two-sided p-value is unstratified as there are too few events per stratum to perform a stratified test.
	Method	Non-stratified log-rank test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lapatinib 1500 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratios were estimated using a Pike estimator.

2. Secondary Outcome

Title	Overall Survival (OS)
Description	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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	342	346
Median (95% Confidence Interval) [Months]	NA	NA

3. Secondary Outcome

Title	Disease Specific Survival (DSS)
Description	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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	342	346
Median (95% Confidence Interval) [Months]	NA	NA

4. Secondary Outcome

Title	Time to Locoregional Recurrence (TTLR)
Description	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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	342	346
Median (95% Confidence Interval) [Months]	NA	NA

5. Secondary Outcome

Title	Time to Distant Relapse (TTDR)
Description	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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	342	346
Median (95% Confidence Interval) [Months]	NA	NA

6. Secondary Outcome

Title	Number of Participants With a Second Primary Tumor
Description	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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	342	346
Number [Participants]	5 1.5%	9 2.6%

7. Secondary Outcome

Title	Extent of Exposure
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Monotherapy, n=332, 347	0.9 (0.32)	0.9 (0.27)
Chemoradiotherapy, n=327, 344	6.6 (1.29)	6.5 (1.58)
Maintenance, n=309, 321	41.5 (20.00)	41.1 (21.03)

8. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Any AE	328 95.9%	344 99.4%
Any SAE	133 38.9%	169 48.8%

9. Secondary Outcome

Title	Number of Participants With the Indicated Chemistry Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Albumin, Grade 3, n=330, 343	1 0.3%	0 0%
Albumin, Grade 4, n=330, 343	0 0%	0 0%
AP, Grade 3, n=333, 347	1 0.3%	2 0.6%
AP, Grade 4, n=333, 347	0 0%	0 0%
ALT, Grade 3, n=333, 348	9 2.6%	3 0.9%
ALT, Grade 4, n=333, 348	1 0.3%	0 0%
AST, Grade 3, n=333, 347	5 1.5%	5 1.4%
AST, Grade 4, n=333, 347	1 0.3%	0 0%
TB, Grade 3, n=333, 348	3 0.9%	6 1.7%
TB, Grade 4, n=333, 348	0 0%	0 0%
Hypercalcemia , Grade 3, n=333, 348	3 0.9%	1 0.3%
Hypercalcemia , Grade 4, n=333, 348	1 0.3%	1 0.3%
Hypocalcemia , Grade 3, n=333, 348	1 0.3%	7 2%
Hypocalcemia , Grade 4, n=333, 348	1 0.3%	3 0.9%
CO2/HCO3, Grade 3, n=187, 207	0 0%	1 0.3%
CO2/HCO3, Grade 4, n=187, 207	0 0%	0 0%
Creatinine, Grade 3, n=333, 348	3 0.9%	9 2.6%
Creatinine, Grade 4, n=333, 348	2 0.6%	0 0%
Hyperglycemia, Grade 3, n=332, 344	6 1.8%	8 2.3%
Hypergylcemia, Grade 4, n=332, 344	1 0.3%	0 0%
Hypoglycemia, Grade 3, n=332, 344	1 0.3%	1 0.3%
Hypogylcemia, Grade 4, n=332, 344	2 0.6%	2 0.6%
Hyperkalemia, Grade 3, n=333, 348	5 1.5%	8 2.3%
Hyperkalemia, Grade 4, n=333, 348	2 0.6%	2 0.6%
Hypokalemia, Grade 3, n=333, 348	17 5%	35 10.1%
Hypokalemia, Grade 4, n=333, 348	1 0.3%	7 2%
Hypernatremia, Grade 3, n=333, 348	0 0%	0 0%
Hypernatremia, Grade 4, n=333, 348	1 0.3%	1 0.3%
Hyponatremia, Grade 3, n=333, 348	59 17.3%	85 24.6%
Hyponatremia, Grade 4, n=333, 348	11 3.2%	0 0%

10. Secondary Outcome

Title	Number of Participants With the Indicated Hematological Toxicities by Maximum Toxicity Grade (G3 and G4) at the Worst-case On-therapy Visit
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Hemoglobin, Grade 3, n=333, 348	10 2.9%	13 3.8%
Hemoglobin, Grade 4, n=333, 348	0 0%	3 0.9%
Lymphocytes, Grade 3, n=333, 348	203 59.4%	208 60.1%
Lymphocytes, Grade 4, n=333, 348	34 9.9%	48 13.9%
TN, Grade 3, n=333, 348	57 16.7%	47 13.6%
TN, Grade 4, n=333, 348	6 1.8%	13 3.8%
PC, Grade 3, n=333, 348	0 0%	3 0.9%
PC, Grade 4, n=333, 348	2 0.6%	2 0.6%
WBC, Grade 3, n=333, 348	70 20.5%	72 20.8%
WBC, Grade 4, n=333, 348	3 0.9%	6 1.7%

11. Secondary Outcome

Title	Number of Participants With On-therapy and Follow-up Late Radiation Morbidity Events
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Gastrointestinal disorders	25 7.3%	23 6.6%
General disorders	8 2.3%	13 3.8%
Skin and subcutaneous tissue disorders	8 2.3%	13 3.8%
Musculoskeletal and connective tissue	13 3.8%	6 1.7%
Respiratory, thoracic and mediastinal	10 2.9%	7 2%
Injury, poisoning and procedural	13 3.8%	3 0.9%
Nervous system disorders	6 1.8%	8 2.3%
Endocrine disorders	4 1.2%	3 0.9%
Infections and infestations	3 0.9%	4 1.2%
Investigations	3 0.9%	3 0.9%
Vascular disorders	4 1.2%	2 0.6%
Blood and lymphatic system disorders	2 0.6%	1 0.3%
Ear and labyrinth disorders	2 0.6%	1 0.3%
Metabolism and nutrition disorders	0 0%	1 0.3%
Neoplasm benign, malignant and unspecified	1 0.3%	0 0%

12. Secondary Outcome

Title	Change From Baseline in Blood Pressure at the Indicated Time Points
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
SBP, Week 1, n=312, 339	-0.29 (14.153)	1.24 (14.273)
SBP, Week 2, n=303, 327	-2.40 (13.815)	-1.56 (16.415)
SBP, Week 3, n=310, 319	-2.64 (14.784)	-1.62 (15.046)
SBP, Week 4, n=312, 319	-4.32 (15.414)	-2.63 (17.044)
SBP, Week 5, n=302, 303	-4.05 (15.490)	-3.09 (16.472)
SBP, Week 6, n=307, 307	-4.70 (15.571)	-4.07 (15.726)
SBP, Week 7, n=282, 289	-4.06 (14.774)	-4.86 (17.046)
SBP, End of CRT, n=304, 310	-4.79 (15.216)	-4.69 (16.692)
SBP, MW 8, n=280, 279	-2.80 (14.137)	-3.58 (15.030)
SBP, MW 16, n=257, 270	-2.86 (15.251)	-2.44 (15.718)
SBP, MW 24, n=234, 252	-3.44 (15.918)	-2.48 (15.793)
SBP, MW 32, n=212, 237	-1.71 (14.936)	-2.55 (15.470)
SBP, MW 40, n=202, 222	-1.76 (14.979)	-1.84 (17.358)
SBP, MW 48, n=199, 210	-1.57 (15.531)	-1.79 (15.700)
SBP, MW 56, n=188, 204	-1.53 (13.942)	-1.64 (15.878)
SBP, Withdrawal from IP, n=99, 84	-2.54 (15.746)	-1.38 (17.895)
DBP, Week 1, n=312, 339	-0.07 (9.214)	0.63 (9.719)
DBP, Week 2, n=303, 327	-0.81 (8.690)	-0.24 (9.933)
DBP, Week 3, n=310, 319	-0.46 (9.245)	-0.68 (9.704)
DBP, Week 4, n=312, 319	-2.54 (9.929)	-2.03 (9.797)
DBP, Week 5, n=302, 303	-1.38 (10.100)	-1.60 (9.679)
DBP, Week 6, n=307, 307	-1.85 (10.673)	-2.37 (9.514)
DBP, Week 7, n=282, 289	-1.73 (11.095)	-2.93 (9.402)
DBP, End of CRT, n=304, 310	-1.97 (10.224)	-2.11 (10.117)
DBP, MW 8, n=280, 279	-0.80 (9.598)	-1.17 (9.877)
DBP, MW 16, n=257, 270	-0.36 (9.980)	-0.98 (9.527)
DBP, MW 24, n=234, 252	-1.26 (9.956)	-1.65 (9.842)
DBP, MW 32, n=212, 237	-0.38 (9.677)	-1.34 (9.929)
DBP, MW 40, n=202, 222	-0.69 (9.809)	-0.69 (11.540)
DBP, MW 48, n=199, 210	0.34 (10.797)	-0.56 (10.057)
DBP, MW 56, n=188, 204	0.20 (9.721)	-0.47 (10.475)
DBP, Withdrawal from IP, n=99, 84	-0.27 (10.256)	-0.85 (11.806)

13. Secondary Outcome

Title	Change From Baseline in Heart Rate at the Indicated Time Points
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Week 1, n=312, 337	-0.18 (10.414)	-0.84 (10.710)
Week 2, n=303, 326	-0.99 (10.910)	-1.17 (10.258)
Week 3, n=306, 319	-0.45 (10.701)	-1.24 (9.766)
Week 4, n=307, 318	-0.86 (11.116)	-0.39 (11.645)
Week 5, n=298, 303	-0.68 (11.673)	-0.39 (11.588)
Week 6, n=306, 306	-0.73 (11.933)	-0.43 (10.947)
Week 7, n=279, 288	1.22 (11.491)	0.40 (11.184)
End of CRT, n=300, 310	0.33 (12.362)	0.54 (11.683)
MW 8, n=279, 277	-0.30 (10.684)	0.85 (10.632)
MW 16, n=256, 268	-1.10 (11.238)	-0.96 (11.129)
MW 24, n=235, 251	-0.98 (11.180)	-1.16 (9.793)
MW 32, n=213, 238	-1.43 (11.934)	-1.24 (10.549)
MW 40, n=203, 222	-2.72 (11.781)	-0.96 (10.556)
MW 48, n=200, 210	-2.56 (12.158)	-0.93 (11.659)
MW 56, n=189, 204	-3.08 (12.056)	-1.16 (11.331)
Withdrawal from IP, n=99, 83	0.02 (12.719)	-0.69 (11.822)

14. Secondary Outcome

Title	Change From Baseline in Body Temperature at the Indicated Time Points
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Week 1, n=308, 331	-0.03 (0.420)	-0.01 (0.436)
Week 2, n=303, 321	-0.01 (0.492)	0.01 (0.410)
Week 3, n=308, 315	0.02 (0.504)	0.01 (0.431)
Week 4, n=306, 317	0.02 (0.511)	0.04 (0.494)
Week 5, n=300, 303	-0.00 (0.514)	0.03 (0.416)
Week 6, n=301, 302	0.06 (0.586)	0.02 (0.540)
Week 7, n=277, 288	0.02 (0.526)	0.06 (0.507)
End of CRT, n=297, 305	0.04 (0.545)	0.03 (0.469)
MW 8, n=274, 273	0.02 (0.529)	0.01 (0.442)
MW 16, n=253, 263	-0.02 (0.525)	-0.03 (0.400)
MW 24, n=227, 244	-0.03 (0.516)	0.04 (0.425)
MW 32, n=207, 235	-0.04 (0.559)	-0.02 (0.453)
MW 40, n=199, 219	-0.04 (0.542)	-0.00 (0.429)
MW 48, n=195, 205	-0.02 (0.645)	-0.01 (0.464)
MW 56, n=184, 200	-0.01 (0.563)	-0.02 (0.466)
Withdrawal from IP, n=97, 78	0.00 (0.562)	0.03 (0.419)

15. Secondary Outcome

Title	Change From Baseline in Body Weight at the Indicated Time Points
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
Week 1, n=317, 343	0.28 (2.301)	-0.04 (2.263)
Week 2, n=314, 336	-0.39 (2.320)	-0.90 (2.747)
Week 3, n=319, 328	-1.01 (2.638)	-1.46 (2.889)
Week 4, n=316, 324	-1.74 (3.116)	-2.24 (3.352)
Week 5, n=307, 309	-2.46 (3.424)	-3.30 (3.803)
Week 6, n=314, 307	-3.22 (3.868)	-4.15 (3.912)
Week 7, n=290, 297	-4.21 (4.072)	-4.94 (4.266)
End of CRT, n=309, 311	-4.54 (4.566)	-5.36 (4.406)
MW 8, n=287, 287	-4.56 (5.851)	-5.67 (5.326)
MW 16, n=257, 275	-4.31 (6.521)	-5.64 (6.120)
MW 24, n=236, 252	-4.26 (7.251)	-5.15 (6.723)
MW 32, n=220, 241	-4.17 (7.685)	-4.73 (6.711)
MW 40, n=208, 224	-3.63 (7.889)	-4.24 (7.348)
MW 48, n=197, 212	-3.20 (7.951)	-3.44 (7.087)
MW 56, n=191, 206	-2.95 (8.427)	-3.47 (7.440)
Withdrawal from IP, n=106, 86	-4.21 (6.785)	-4.81 (7.649)

16. Secondary Outcome

Title	Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
BL, Abnormal NCS, n=334, 349	82 24%	78 22.5%
BL, Abnormal CS, n=334, 349	1 0.3%	0 0%
End of CRT, Abnormal NCS, n=287, 292	76 22.2%	71 20.5%
End of CRT, Abnormal CS, n=287, 292	2 0.6%	2 0.6%
Maintenance Week 56, Abnormal NCS, n=166, 174	32 9.4%	32 9.2%
Maintenance Week 56, Abnormal CS, n=166, 174	2 0.6%	0 0%
Withdrawal from IP, Abnormal NCS, n=70, 59	16 4.7%	12 3.5%
Withdrawal from IP, Abnormal CS, n=70, 59	1 0.3%	1 0.3%
Anytime post-baseline, Abnormal NCS, n=307, 312	94 27.5%	88 25.4%
Anytime post-baseline, Abnormal CS, n=307, 312	4 1.2%	3 0.9%

17. Secondary Outcome

Title	Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	336	349
BL, ECOG 0, n=336, 349	173 50.6%	179 51.7%
BL, ECOG 1, n=336, 349	161 47.1%	157 45.4%
BL, ECOG 2, n=336, 349	2 0.6%	13 3.8%
Week 1, ECOG 0, n=319, 342	160 46.8%	174 50.3%
Week 1, ECOG 1, n=319, 342	156 45.6%	159 46%
Week 1, ECOG 2, n=319, 342	3 0.9%	9 2.6%
Week 1, ECOG 3, n=319, 342	0 0%	0 0%
Week 1, ECOG 4-5, n=319, 342	0 0%	0 0%
Week 2, ECOG 0, n=313, 333	142 41.5%	149 43.1%
Week 2, ECOG 1, n=313, 333	166 48.5%	168 48.6%
Week 2, ECOG 2, n=313, 333	5 1.5%	16 4.6%
Week 2, ECOG 3, n=313, 333	0 0%	0 0%
Week 2, ECOG 4-5, n=313, 333	0 0%	0 0%
Week 3, ECOG 0, n=310, 329	138 40.4%	131 37.9%
Week 3, ECOG 1, n=310, 329	169 49.4%	183 52.9%
Week 3, ECOG 2, n=310, 329	3 0.9%	15 4.3%
Week 3, ECOG 3, n=310, 329	0 0%	0 0%
Week 3, ECOG 4-5, n=310, 329	0 0%	0 0%
Week 4, ECOG 0, n=317, 327	115 33.6%	111 32.1%
Week 4, ECOG 1, n=317, 327	191 55.8%	194 56.1%
Week 4, ECOG 2, n=317, 327	11 3.2%	21 6.1%
Week 4, ECOG 3, n=317, 327	0 0%	1 0.3%
Week 4, ECOG 4-5, n=317, 327	0 0%	0 0%
Week 5, ECOG 0, n=307, 312	100 29.2%	95 27.5%
Week 5, ECOG 1, n=307, 312	191 55.8%	183 52.9%
Week 5, ECOG 2, n=307, 312	16 4.7%	30 8.7%
Week 5, ECOG 3, n=307, 312	0 0%	4 1.2%
Week 5, ECOG 4-5, n=307, 312	0 0%	0 0%
Week 6, ECOG 0, n=312, 309	97 28.4%	88 25.4%
Week 6, ECOG 1, n=312, 309	187 54.7%	186 53.8%
Week 6, ECOG 2, n=312, 309	26 7.6%	32 9.2%
Week 6, ECOG 3, n=312, 309	2 0.6%	3 0.9%
Week 6, ECOG 4-5, n=312, 309	0 0%	0 0%
Week 7, ECOG 0, n=284, 295	83 24.3%	88 25.4%
Week 7, ECOG 1, n=284, 295	175 51.2%	176 50.9%
Week 7, ECOG 2, n=284, 295	23 6.7%	30 8.7%
Week 7, ECOG 3, n=284, 295	3 0.9%	1 0.3%
Week 7, ECOG 4-5, n=284, 295	0 0%	0 0%
End of CRT, ECOG 0, n=307, 315	95 27.8%	84 24.3%
End of CRT, ECOG 1, n=307, 315	184 53.8%	186 53.8%
End of CRT, ECOG 2, n=307, 315	25 7.3%	45 13%
End of CRT, ECOG 3, n=307, 315	3 0.9%	0 0%
End of CRT, ECOG 4-5, n=307, 315	0 0%	0 0%
Maintenance week 8, ECOG 0, n=286, 290	132 38.6%	128 37%
Maintenance week 8, ECOG 1, n=286, 290	146 42.7%	153 44.2%
Maintenance week 8, ECOG 2, n=286, 290	7 2%	9 2.6%
Maintenance week 8, ECOG 3, n=286, 290	1 0.3%	0 0%
Maintenance week 8, ECOG 4-5, n=286, 290	0 0%	0 0%
Maintenance week 16, ECOG 0, n=260, 273	135 39.5%	129 37.3%
Maintenance week 16, ECOG 1, n=260, 273	124 36.3%	138 39.9%
Maintenance week 16, ECOG 2, n=260, 273	1 0.3%	6 1.7%
Maintenance week 16, ECOG 3, n=260, 273	0 0%	0 0%
Maintenance week 16, ECOG 4-5, n=260, 273	0 0%	0 0%
Maintenance week 24, ECOG 0, n=235, 251	122 35.7%	127 36.7%
Maintenance week 24, ECOG 1, n=235, 251	110 32.2%	119 34.4%
Maintenance week 24, ECOG 2, n=235, 251	3 0.9%	5 1.4%
Maintenance week 24, ECOG 3, n=235, 251	0 0%	0 0%
Maintenance week 24, ECOG 4-5, n=235, 251	0 0%	0 0%
Maintenance week 32, ECOG 0, n=218, 241	117 34.2%	123 35.5%
Maintenance week 32, ECOG 1, n=218, 241	99 28.9%	115 33.2%
Maintenance week 32, ECOG 2, n=218, 241	2 0.6%	1 0.3%
Maintenance week 32, ECOG 3, n=218, 241	0 0%	2 0.6%
Maintenance week 32, ECOG 4-5, n=218, 241	0 0%	0 0%
Maintenance week 40, ECOG 0, n=208, 227	118 34.5%	130 37.6%
Maintenance week 40, ECOG 1, n=208, 227	88 25.7%	94 27.2%
Maintenance week 40, ECOG 2, n=208, 227	2 0.6%	2 0.6%
Maintenance week 40, ECOG 3, n=208, 227	0 0%	1 0.3%
Maintenance week 40, ECOG 4-5, n=208, 227	0 0%	0 0%
Maintenance week 48, ECOG 0, n=205, 214	121 35.4%	111 32.1%
Maintenance week 48, ECOG 1, n=205, 214	81 23.7%	102 29.5%
Maintenance week 48, ECOG 2, n=205, 214	3 0.9%	1 0.3%
Maintenance week 48, ECOG 3, n=205, 214	0 0%	0 0%
Maintenance week 48, ECOG 4-5, n=205, 214	0 0%	0 0%
Maintenance week 56, ECOG 0, n=194, 211	107 31.3%	111 32.1%
Maintenance week 56, ECOG 1, n=194, 211	85 24.9%	98 28.3%
Maintenance week 56, ECOG 2, n=194, 211	2 0.6%	2 0.6%
Maintenance week 56, ECOG 3, n=194, 211	0 0%	0 0%
Maintenance week 56, ECOG 4-5, n=194, 211	0 0%	0 0%
Withdrawal from IP, ECOG 0, n=109, 92	44 12.9%	38 11%
Withdrawal from IP, ECOG 1, n=109, 92	50 14.6%	40 11.6%
Withdrawal from IP, ECOG 2, n=109, 92	12 3.5%	11 3.2%
Withdrawal from IP, ECOG 3, n=109, 92	2 0.6%	1 0.3%
Withdrawal from IP, ECOG 4-5, n=109, 92	1 0.3%	2 0.6%
Last assessment on therapy, ECOG 0, n=334, 348	153 44.7%	154 44.5%
Last assessment on therapy, ECOG 1, n=334, 348	158 46.2%	165 47.7%
Last assessment on therapy, ECOG 2, n=334, 348	19 5.6%	22 6.4%
Last assessment on therapy, ECOG 3, n=334, 348	3 0.9%	5 1.4%
Last assessment on therapy, ECOG 4-5, n=334, 348	1 0.3%	2 0.6%

18. Secondary Outcome

Title	Change From Baseline in Quality of Life Status as Assessed by the Functional Assessement of Cancer Therapy-Head and Neck (FACT-H&N) Questionnaire
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had a Baseline and post-Baseline score at the specified time points were analyzed.

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	171	189
Physical Well-being, n=171, 188	0.4 (0.33)	-0.1 (0.31)
Social/Family Well-being, n=171, 189	-0.3 (0.36)	-1.7 (0.34)
Emotional Well-being, n=169, 187	1.0 (0.27)	0.0 (0.26)
Functional Well-being, n=168, 188	0.9 (0.39)	-0.4 (0.37)
Head and Neck Cancer subscale, n=168, 189	-1.2 (0.43)	-1.7 (0.40)

19. Secondary Outcome

Title	Change From Baseline in Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had a Baseline and post-Baseline score at the specified time points were analyzed.

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	173	187
Utility score, n=172, 186	0.1 (0.01)	0.0 (0.01)
Thermometer score, n=173, 197	5.5 (1.29)	3.2 (1.25)

20. Secondary Outcome

Title	Number of Participants With the Indicated Biomarker Expression Status
Description	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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	342	346
P16, Positive	42 12.3%	48 13.9%
P16, Negative	282 82.5%	271 78.3%
P16, Unknown	18 5.3%	27 7.8%
Overall HPV, Positive	21 6.1%	23 6.6%
Overall HPV, Negative	284 83%	276 79.8%
Overall HPV, Unknown	37 10.8%	47 13.6%
ErbB1, Positive	330 96.5%	338 97.7%
ErbB1, Negative	12 3.5%	8 2.3%

21. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Left Ventricular Ejection Fraction (LVEF) Change From Baseline
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	Lapatinib 1500 mg
Arm/Group Description	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.	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.
Measure Participants	309	311
Abs, No change/any increase	102 29.8%	90 26%
Abs, >0 to <10% decrease	138 40.4%	131 37.9%
Abs, 10 to 19% decrease	65 19%	80 23.1%
Abs, >=20% decrease	4 1.2%	10 2.9%
Abs, >=10% decrease and >=LLN	62 18.1%	69 19.9%
Abs, >=10% decrease and below LLN	7 2%	21 6.1%
Abs, >=20% decrease and >=LLN	3 0.9%	5 1.4%
Abs, >=20% decrease and below LLN	1 0.3%	5 1.4%
Rel, >=20% decrease and >=LLN	22 6.4%	18 5.2%
Rel, >=20% decrease and below LLN	3 0.9%	14 4%

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up of treatment (average of 141 study weeks).
Adverse Event Reporting Description	SAEs and non-serious AEs were reported for members of the Safety Population, comprised of all participants who were randomized and took at least one dose of study medication. Participants randomized to placebo who received >=1 dose of lapatinib in error were included in the lapatinib arm.
Arm/Group Title	Placebo		Lapatinib 1500 mg
Arm/Group Description	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.		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.
All Cause Mortality
	Placebo		Lapatinib 1500 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Lapatinib 1500 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	133/336 (39.6%)		169/349 (48.4%)
Blood and lymphatic system disorders
Lymphopenia	17/336 (5.1%)		18/349 (5.2%)
Neutropenia	10/336 (3%)		10/349 (2.9%)
Anaemia	2/336 (0.6%)		7/349 (2%)
Febrile neutropenia	4/336 (1.2%)		5/349 (1.4%)
Leukopenia	5/336 (1.5%)		4/349 (1.1%)
Thrombocytopenia	3/336 (0.9%)		2/349 (0.6%)
Bone marrow failure	0/336 (0%)		1/349 (0.3%)
Disseminated intravascular coagulation	1/336 (0.3%)		0/349 (0%)
Haematotoxicity	0/336 (0%)		1/349 (0.3%)
Cardiac disorders
Cardiac arrest	2/336 (0.6%)		1/349 (0.3%)
Left ventricular dysfunction	0/336 (0%)		2/349 (0.6%)
Acute myocardial infarction	0/336 (0%)		1/349 (0.3%)
Atrial fibrillation	1/336 (0.3%)		0/349 (0%)
Cardiac failure acute	0/336 (0%)		1/349 (0.3%)
Cardio-respiratory arrest	1/336 (0.3%)		0/349 (0%)
Diastolic dysfunction	0/336 (0%)		1/349 (0.3%)
Intracardiac mass	0/336 (0%)		1/349 (0.3%)
Palpitations	0/336 (0%)		1/349 (0.3%)
Ventricular hypokinesia	1/336 (0.3%)		0/349 (0%)
Cardiopulmonary failure	0/336 (0%)		1/349 (0.3%)
Congenital, familial and genetic disorders
Aplasia	0/336 (0%)		1/349 (0.3%)
Ear and labyrinth disorders
Hypoacusis	1/336 (0.3%)		0/349 (0%)
Neurosensory hypoacusis	0/336 (0%)		1/349 (0.3%)
Endocrine disorders
Hypothyroidism	1/336 (0.3%)		0/349 (0%)
Eye disorders
Conjunctival haemorrhage	0/336 (0%)		1/349 (0.3%)
Periorbital oedema	0/336 (0%)		1/349 (0.3%)
Gastrointestinal disorders
Vomiting	8/336 (2.4%)		12/349 (3.4%)
Dysphagia	5/336 (1.5%)		11/349 (3.2%)
Nausea	3/336 (0.9%)		7/349 (2%)
Diarrhoea	3/336 (0.9%)		6/349 (1.7%)
Stomatitis	5/336 (1.5%)		4/349 (1.1%)
Oesophageal stenosis	1/336 (0.3%)		3/349 (0.9%)
Mouth haemorrhage	1/336 (0.3%)		2/349 (0.6%)
Oral pain	1/336 (0.3%)		1/349 (0.3%)
Anal fistula	0/336 (0%)		1/349 (0.3%)
Constipation	1/336 (0.3%)		0/349 (0%)
Dyspepsia	0/336 (0%)		1/349 (0.3%)
Gastric perforation	0/336 (0%)		1/349 (0.3%)
Gastrooesophagitis	0/336 (0%)		1/349 (0.3%)
Haematemesis	0/336 (0%)		1/349 (0.3%)
Oesophageal fistula	1/336 (0.3%)		0/349 (0%)
Oesophagitis ulcerative	0/336 (0%)		1/349 (0.3%)
Pancreatitis	0/336 (0%)		1/349 (0.3%)
Pancreatitis acute	1/336 (0.3%)		0/349 (0%)
Retroperitoneal haemorrhage	1/336 (0.3%)		0/349 (0%)
Stomatitis haemorrhagic	0/336 (0%)		1/349 (0.3%)
General disorders
Mucosal inflammation	9/336 (2.7%)		17/349 (4.9%)
Pyrexia	5/336 (1.5%)		6/349 (1.7%)
General physical health deterioration	6/336 (1.8%)		4/349 (1.1%)
Asthenia	3/336 (0.9%)		4/349 (1.1%)
Death	1/336 (0.3%)		4/349 (1.1%)
Fatigue	2/336 (0.6%)		2/349 (0.6%)
Impaired healing	1/336 (0.3%)		1/349 (0.3%)
Malaise	2/336 (0.6%)		0/349 (0%)
Medical device complication	1/336 (0.3%)		1/349 (0.3%)
Catheter site discharge	1/336 (0.3%)		0/349 (0%)
Catheter site related reaction	0/336 (0%)		1/349 (0.3%)
Disease progression	0/336 (0%)		1/349 (0.3%)
Face oedema	0/336 (0%)		1/349 (0.3%)
Mucosal induration	0/336 (0%)		1/349 (0.3%)
Non-cardiac chest pain	0/336 (0%)		1/349 (0.3%)
Performance status decreased	1/336 (0.3%)		0/349 (0%)
Sudden death	0/336 (0%)		1/349 (0.3%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/336 (0.3%)		2/349 (0.6%)
Infections and infestations
Pneumonia	4/336 (1.2%)		6/349 (1.7%)
Sepsis	2/336 (0.6%)		4/349 (1.1%)
Wound infection	0/336 (0%)		3/349 (0.9%)
Bronchopneumonia	1/336 (0.3%)		1/349 (0.3%)
Erysipelas	2/336 (0.6%)		0/349 (0%)
Gastroenteritis	1/336 (0.3%)		1/349 (0.3%)
Lung abscess	0/336 (0%)		2/349 (0.6%)
Lung infection	1/336 (0.3%)		1/349 (0.3%)
Neutropenic sepsis	1/336 (0.3%)		1/349 (0.3%)
Oral infection	0/336 (0%)		2/349 (0.6%)
Abscess limb	0/336 (0%)		1/349 (0.3%)
Abscess neck	1/336 (0.3%)		0/349 (0%)
Bacteraemia	0/336 (0%)		1/349 (0.3%)
Blister infected	1/336 (0.3%)		0/349 (0%)
Catheter site infection	0/336 (0%)		1/349 (0.3%)
Cellulitis	1/336 (0.3%)		0/349 (0%)
Febrile infection	0/336 (0%)		1/349 (0.3%)
Lobar pneumonia	1/336 (0.3%)		0/349 (0%)
Lower respiratory tract infection	1/336 (0.3%)		0/349 (0%)
Osteomyelitis	1/336 (0.3%)		0/349 (0%)
Otitis media	1/336 (0.3%)		0/349 (0%)
Paraoesophageal abscess	0/336 (0%)		1/349 (0.3%)
Parotid abscess	1/336 (0.3%)		0/349 (0%)
Perichondritis	1/336 (0.3%)		0/349 (0%)
Pulmonary tuberculosis	0/336 (0%)		1/349 (0.3%)
Pyelonephritis	0/336 (0%)		1/349 (0.3%)
Respiratory tract infection	0/336 (0%)		1/349 (0.3%)
Sepsis syndrome	1/336 (0.3%)		0/349 (0%)
Septic shock	1/336 (0.3%)		0/349 (0%)
Streptococcal sepsis	1/336 (0.3%)		0/349 (0%)
Superinfection	1/336 (0.3%)		0/349 (0%)
Tooth abscess	1/336 (0.3%)		0/349 (0%)
Tooth infection	1/336 (0.3%)		0/349 (0%)
Tracheitis	0/336 (0%)		1/349 (0.3%)
Urinary tract infection	1/336 (0.3%)		0/349 (0%)
Hepatitis E	0/336 (0%)		1/349 (0.3%)
Injury, poisoning and procedural complications
Osteoradionecrosis	6/336 (1.8%)		1/349 (0.3%)
Tracheostomy malfunction	1/336 (0.3%)		3/349 (0.9%)
Radiation mucositis	1/336 (0.3%)		2/349 (0.6%)
Fall	1/336 (0.3%)		1/349 (0.3%)
Anastomotic stenosis	1/336 (0.3%)		0/349 (0%)
Ankle fracture	1/336 (0.3%)		0/349 (0%)
Feeding tube complication	1/336 (0.3%)		0/349 (0%)
Femur fracture	1/336 (0.3%)		0/349 (0%)
Fibula fracture	0/336 (0%)		1/349 (0.3%)
Foreign body	1/336 (0.3%)		0/349 (0%)
Implant tissue necrosis	0/336 (0%)		1/349 (0.3%)
Limb injury	0/336 (0%)		1/349 (0.3%)
Post procedural haemorrhage	1/336 (0.3%)		0/349 (0%)
Radiation sickness syndrome	1/336 (0.3%)		0/349 (0%)
Tibia fracture	0/336 (0%)		1/349 (0.3%)
Traumatic fracture	1/336 (0.3%)		0/349 (0%)
Upper limb fracture	0/336 (0%)		1/349 (0.3%)
Wound complication	0/336 (0%)		1/349 (0.3%)
Wound dehiscence	1/336 (0.3%)		0/349 (0%)
Investigations
Ejection fraction decreased	3/336 (0.9%)		10/349 (2.9%)
Blood creatinine increased	2/336 (0.6%)		5/349 (1.4%)
Hepatic enzyme increased	2/336 (0.6%)		3/349 (0.9%)
Weight decreased	1/336 (0.3%)		4/349 (1.1%)
Alanine aminotransferase increased	3/336 (0.9%)		1/349 (0.3%)
Blood uric acid increased	1/336 (0.3%)		2/349 (0.6%)
Aspartate aminotransferase increased	2/336 (0.6%)		0/349 (0%)
Glomerular filtration rate decreased	1/336 (0.3%)		1/349 (0.3%)
Alanine aminotransferase abnormal	0/336 (0%)		1/349 (0.3%)
Blood bilirubin abnormal	0/336 (0%)		1/349 (0.3%)
Calcium ionised decreased	0/336 (0%)		1/349 (0.3%)
Electrocardiogram abnormal	0/336 (0%)		1/349 (0.3%)
Electrocardiogram change	0/336 (0%)		1/349 (0.3%)
Gamma-glutamyltransferase increased	0/336 (0%)		1/349 (0.3%)
Metabolism and nutrition disorders
Hyponatraemia	6/336 (1.8%)		12/349 (3.4%)
Dehydration	5/336 (1.5%)		6/349 (1.7%)
Hyperuricaemia	4/336 (1.2%)		3/349 (0.9%)
Hypokalaemia	2/336 (0.6%)		5/349 (1.4%)
Decreased appetite	3/336 (0.9%)		3/349 (0.9%)
Malnutrition	2/336 (0.6%)		4/349 (1.1%)
Electrolyte imbalance	2/336 (0.6%)		1/349 (0.3%)
Hypercalcaemia	2/336 (0.6%)		1/349 (0.3%)
Hyperkalaemia	0/336 (0%)		3/349 (0.9%)
Hypocalcaemia	0/336 (0%)		3/349 (0.9%)
Feeding disorder	0/336 (0%)		2/349 (0.6%)
Hypernatraemia	0/336 (0%)		1/349 (0.3%)
Hypophagia	0/336 (0%)		1/349 (0.3%)
Metabolic disorder	0/336 (0%)		1/349 (0.3%)
Musculoskeletal and connective tissue disorders
Neck pain	1/336 (0.3%)		2/349 (0.6%)
Osteonecrosis	3/336 (0.9%)		0/349 (0%)
Fistula	1/336 (0.3%)		1/349 (0.3%)
Back pain	0/336 (0%)		1/349 (0.3%)
Joint range of motion decreased	0/336 (0%)		1/349 (0.3%)
Myalgia	1/336 (0.3%)		1/349 (0.3%)
Pain in jaw	1/336 (0.3%)		0/349 (0%)
Pathological fracture	1/336 (0.3%)		0/349 (0%)
Temporomandibular joint syndrome	1/336 (0.3%)		0/349 (0%)
Trismus	0/336 (0%)		1/349 (0.3%)
Trismus	1/336 (0.3%)		1/349 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/336 (0.3%)		0/349 (0%)
Breast cancer	0/336 (0%)		1/349 (0.3%)
Bronchial carcinoma	0/336 (0%)		1/349 (0.3%)
Lung neoplasm	0/336 (0%)		1/349 (0.3%)
Lung neoplasm malignant	0/336 (0%)		1/349 (0.3%)
Neoplasm recurrence	1/336 (0.3%)		0/349 (0%)
Oesophageal carcinoma	1/336 (0.3%)		0/349 (0%)
Oesophageal neoplasm	1/336 (0.3%)		0/349 (0%)
Oral fibroma	1/336 (0.3%)		0/349 (0%)
Pancreatic carcinoma	1/336 (0.3%)		0/349 (0%)
Prostate cancer	1/336 (0.3%)		0/349 (0%)
Second primary malignancy	0/336 (0%)		1/349 (0.3%)
Oral neoplasm	0/336 (0%)		1/349 (0.3%)
Squamous cell carcinoma of the oral cavity	0/336 (0%)		1/349 (0.3%)
Testis cancer	0/336 (0%)		1/349 (0.3%)
Nervous system disorders
Syncope	2/336 (0.6%)		1/349 (0.3%)
Cerebral ischaemia	0/336 (0%)		2/349 (0.6%)
Ataxia	0/336 (0%)		1/349 (0.3%)
Brain hypoxia	1/336 (0.3%)		0/349 (0%)
Brain injury	0/336 (0%)		1/349 (0.3%)
Cerebral infarction	1/336 (0.3%)		0/349 (0%)
Convulsion	1/336 (0.3%)		0/349 (0%)
Dizziness	0/336 (0%)		1/349 (0.3%)
Dysgeusia	0/336 (0%)		1/349 (0.3%)
Dyskinesia	1/336 (0.3%)		0/349 (0%)
Grand mal convulsion	0/336 (0%)		1/349 (0.3%)
Paralysis	0/336 (0%)		1/349 (0.3%)
Subarachnoid haemorrhage	1/336 (0.3%)		0/349 (0%)
Psychiatric disorders
Depression	1/336 (0.3%)		2/349 (0.6%)
Completed suicide	1/336 (0.3%)		1/349 (0.3%)
Suicide attempt	1/336 (0.3%)		1/349 (0.3%)
Confusional state	1/336 (0.3%)		0/349 (0%)
Renal and urinary disorders
Renal failure	1/336 (0.3%)		3/349 (0.9%)
Renal failure acute	3/336 (0.9%)		0/349 (0%)
Renal impairment	1/336 (0.3%)		2/349 (0.6%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/336 (0.6%)		2/349 (0.6%)
Dyspnoea	1/336 (0.3%)		3/349 (0.9%)
Pharyngeal fistula	2/336 (0.6%)		2/349 (0.6%)
Pneumonia aspiration	2/336 (0.6%)		2/349 (0.6%)
Pulmonary embolism	3/336 (0.9%)		1/349 (0.3%)
Laryngeal oedema	3/336 (0.9%)		0/349 (0%)
Epistaxis	0/336 (0%)		2/349 (0.6%)
Haemoptysis	1/336 (0.3%)		1/349 (0.3%)
Laryngeal stenosis	1/336 (0.3%)		1/349 (0.3%)
Pneumonitis	1/336 (0.3%)		1/349 (0.3%)
Respiratory disorder	1/336 (0.3%)		1/349 (0.3%)
Respiratory distress	2/336 (0.6%)		0/349 (0%)
Aspiration	0/336 (0%)		1/349 (0.3%)
Chronic obstructive pulmonary disease	0/336 (0%)		1/349 (0.3%)
Cough	1/336 (0.3%)		0/349 (0%)
Dysphonia	0/336 (0%)		1/349 (0.3%)
Laryngeal disorder	1/336 (0.3%)		0/349 (0%)
Lung disorder	0/336 (0%)		1/349 (0.3%)
Pharyngeal inflammation	1/336 (0.3%)		0/349 (0%)
Pharyngeal stenosis	0/336 (0%)		1/349 (0.3%)
Pleural effusion	1/336 (0.3%)		0/349 (0%)
Pleurisy	1/336 (0.3%)		0/349 (0%)
Pneumothorax	1/336 (0.3%)		0/349 (0%)
Respiratory failure	1/336 (0.3%)		0/349 (0%)
Skin and subcutaneous tissue disorders
Rash	2/336 (0.6%)		4/349 (1.1%)
Skin reaction	3/336 (0.9%)		0/349 (0%)
Ecchymosis	1/336 (0.3%)		0/349 (0%)
Pemphigus	1/336 (0.3%)		0/349 (0%)
Swelling face	0/336 (0%)		1/349 (0.3%)
Vascular disorders
Haematoma	1/336 (0.3%)		1/349 (0.3%)
Hypertension	2/336 (0.6%)		0/349 (0%)
Arterial rupture	1/336 (0.3%)		0/349 (0%)
Arterial thrombosis	1/336 (0.3%)		0/349 (0%)
Deep vein thrombosis	1/336 (0.3%)		0/349 (0%)
Femoral artery occlusion	1/336 (0.3%)		0/349 (0%)
Haemorrhage	0/336 (0%)		1/349 (0.3%)
Superior vena cava syndrome	1/336 (0.3%)		0/349 (0%)
Venous thrombosis	0/336 (0%)		1/349 (0.3%)
Venous thrombosis limb	1/336 (0.3%)		0/349 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Lapatinib 1500 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	321/336 (95.5%)		337/349 (96.6%)
Blood and lymphatic system disorders
Anaemia	61/336 (18.2%)		77/349 (22.1%)
Leukopenia	99/336 (29.5%)		83/349 (23.8%)
Lymphopenia	75/336 (22.3%)		87/349 (24.9%)
Neutropenia	77/336 (22.9%)		70/349 (20.1%)
Thrombocytopenia	25/336 (7.4%)		24/349 (6.9%)
Gastrointestinal disorders
Constipation	74/336 (22%)		60/349 (17.2%)
Diarrhoea	41/336 (12.2%)		147/349 (42.1%)
Dry mouth	131/336 (39%)		148/349 (42.4%)
Dyspepsia	21/336 (6.3%)		30/349 (8.6%)
Dysphagia	113/336 (33.6%)		125/349 (35.8%)
Nausea	150/336 (44.6%)		181/349 (51.9%)
Odynophagia	34/336 (10.1%)		41/349 (11.7%)
Oral pain	35/336 (10.4%)		25/349 (7.2%)
Stomatitis	50/336 (14.9%)		50/349 (14.3%)
Vomiting	115/336 (34.2%)		154/349 (44.1%)
General disorders
Asthenia	45/336 (13.4%)		59/349 (16.9%)
Fatigue	36/336 (10.7%)		41/349 (11.7%)
Mucosal inflammation	208/336 (61.9%)		220/349 (63%)
Pyrexia	60/336 (17.9%)		63/349 (18.1%)
Infections and infestations
Oral candidiasis	22/336 (6.5%)		17/349 (4.9%)
Injury, poisoning and procedural complications
Radiation mucositis	19/336 (5.7%)		13/349 (3.7%)
Radiation skin injury	79/336 (23.5%)		55/349 (15.8%)
Investigations
Alanine aminotransferase increased	31/336 (9.2%)		30/349 (8.6%)
Aspartate aminotransferase increased	28/336 (8.3%)		33/349 (9.5%)
Blood creatinine increased	33/336 (9.8%)		44/349 (12.6%)
Creatinine renal clearance decreased	17/336 (5.1%)		27/349 (7.7%)
Haemoglobin decreased	29/336 (8.6%)		33/349 (9.5%)
Lymphocyte count decreased	18/336 (5.4%)		20/349 (5.7%)
Weight decreased	64/336 (19%)		90/349 (25.8%)
White blood cell count decreased	23/336 (6.8%)		30/349 (8.6%)
Metabolism and nutrition disorders
Decreased appetite	69/336 (20.5%)		62/349 (17.8%)
Hypokalaemia	28/336 (8.3%)		42/349 (12%)
Hyponatraemia	25/336 (7.4%)		33/349 (9.5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	23/336 (6.8%)		15/349 (4.3%)
Neck pain	28/336 (8.3%)		20/349 (5.7%)
Nervous system disorders
Dysgeusia	45/336 (13.4%)		31/349 (8.9%)
Headache	28/336 (8.3%)		20/349 (5.7%)
Psychiatric disorders
Insomnia	20/336 (6%)		17/349 (4.9%)
Respiratory, thoracic and mediastinal disorders
Cough	37/336 (11%)		45/349 (12.9%)
Dysphonia	21/336 (6.3%)		23/349 (6.6%)
Oropharyngeal pain	67/336 (19.9%)		45/349 (12.9%)
Productive cough	36/336 (10.7%)		25/349 (7.2%)
Skin and subcutaneous tissue disorders
Pruritus	9/336 (2.7%)		23/349 (6.6%)
Rash	101/336 (30.1%)		167/349 (47.9%)
Skin reaction	37/336 (11%)		41/349 (11.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.