Lapatinib Versus Placebo Given Concurrently With Cisplati... | NCT00387127

Label	Type	Description	Intervention Names
Lapatinib	Experimental	1500mg lapatinib orally daily	Drug: Lapatinib oral tablets Drug: radiotherapy Drug: cisplatin chemotherapy
Placebo	Placebo Comparator	orally daily	Drug: Lapatinib oral tablets Drug: radiotherapy Drug: cisplatin chemotherapy

Name	Type	Description	Arm Group Labels	Other Names
Lapatinib oral tablets	Drug	Lapatinib is administered orally once daily.	Lapatinib Placebo

Measure	Description	Time Frame
Number of Participants (Par.) With Complete Response (CR), as Assessed by Independent Radiological Review	Participants with CR are defined as those who achieved a complete tumor response at 6 months after the completion of the chemoradiation treatment (CRT), as assessed by independent radiological review. Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Per RECIST, CR is defined as the disappearance of all target and non-target lesions. Data are based on Week 24 scans from participants receiving study treatment at that time and on those in follow-up.	From the date of randomization until 6 months post chemoradiation treatment, assessed for a median time of 13 months

Measure	Description	Time Frame
Number of Participants With CR, as Assessed by the Investigator	Participants with CR are defined as those who achieved a complete tumor response at 6 months after the completion of the CRT, as determined by the investigator. Tumor response was assessed using modified RECIST criteria. Per RECIST, CR is defined as the disappearance of all target and non-target lesions. Data are based on Week 24 scans from participants receiving study treatment at that time and on those in follow-up.

Measure	Description	Time Frame
Number of Participants Classified as Responders, as Per Volumetric Tumor Response	No analysis was not performed.	From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Minneapolis	Minnesota	55417	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
23265705	Background	Harrington K, Berrier A, Robinson M, Remenar E, Housset M, de Mendoza FH, Fayette J, Mehanna H, El-Hariry I, Compton N, Franklin N, Biswas-Baldwin N, Lau M, Legenne P, Kumar R. Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: rationale for future randomised trials in human papilloma virus-negative disease. Eur J Cancer. 2013 May;49(7):1609-18. doi: 10.1016/j.ejca.2012.11.023. Epub 2012 Dec 19.
25057165

ID	Title	Description
FG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants (Par.) With Complete Response (CR), as Assessed by Independent Radiological Review

Participants with CR are defined as those who achieved a complete tumor response at 6 months after the completion of the chemoradiation treatment (CRT), as assessed by independent radiological review. Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Per RECIST, CR is defined as the disappearance of all target and non-target lesions. Data are based on Week 24 scans from participants receiving study treatment at that time and on those in follow-up.

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

Posted

Number

Participants

From the date of randomization until 6 months post chemoradiation treatment, assessed for a median time of 13 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.

Units	Counts
Participants	OG00033 OG00134

Title

Denominators

Categories

Title	Measurements
	OG00012 OG00118

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		0.3658	From exact test that common odds ratio equals 1	Difference in percentage of par. with CR	10.7			2-Sided	95	-13.4	37.3			Complete response was defined as the percentage of participants achieving a CR as determined by an independent radiological review.	No	Superiority or Other

Secondary

Number of Participants With CR, as Assessed by the Investigator

Participants with CR are defined as those who achieved a complete tumor response at 6 months after the completion of the CRT, as determined by the investigator. Tumor response was assessed using modified RECIST criteria. Per RECIST, CR is defined as the disappearance of all target and non-target lesions. Data are based on Week 24 scans from participants receiving study treatment at that time and on those in follow-up.

ITT Population

Posted

Number

Participants

From the date of randomization until 6 months post chemoradiation treatment, assessed after a median time of 13 months of follow-up

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib

Secondary

Progression-Free Survival (PFS), as Assessed by the Investigator

PFS=the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. Per RECIST, progressive disease=a >=20% increase in the sum of the longest diameter of target lesions (TLs), or the appearance of >=1 new L, symptomatic progression and/or unequivocal progression of existing non-TLs. For participants who did not progress or die at the time of reporting (data cut-off 1-Aug-2014), PFS data were censored at the time of the last investigator assessed radiological scan preceding the initiation of any alternative anti-cancer therapy.

ITT Population

Posted

Median

95% Confidence Interval

Months

From the date of randomization until the date of disease progression or death due to any cause, assessed after a median of 22 months of follow-up

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.

Secondary

Overall Survival (OS)

OS is defined as the time from randomization until death due to any cause. Time to death (data cut-off 1-Aug-2014) was censored at the time of last contact for participants who did not die.

ITT Population

Posted

Median

95% Confidence Interval

Months

From the date of randomization until the date of death due to any cause, assessed after a median of 30.9 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.

Secondary

Number of Participants Who Died Due to Progressive Disease

The number of participants who died due to progressive disease (a >=20% increase in the sum of the longest diameter of target lesions, or the appearance of >=1 new lesion, symptomatic progression and/or unequivocal progression of existing non-target lesions), or died due to head and neck cancer without evidence of disease progression, after randomization in the study is presented, using a data cut of 1 August 2014.

ITT Population

Posted

Number

Participants

From the date of randomization until the date of death due to disease under study, assessed after a median of 30.9 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib

Secondary

Disease-specific Survival

Disease-specific survival is defined as the time from randomization until death due to head and neck cancer.

ITT Population. For participants who did not die, time to death was censored at the time of last contact.

Posted

Median

Inter-Quartile Range

Months

From the date of randomization until the date of death due to disease, assessed after a median of 13 months of follow-up

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.

Secondary

Number of Participants With Loco-regional Recurrence of Initial Disease

Participants with loco-regional recurrence were those who had progression of disease in the T and N sites. Per the Tumor, Node, and Metastases (TNM) staging of tumors: T describes the size of the tumor and whether it has invaded nearby tissue, and N describes regional lymph nodes that are involved. If a participant had progression in the T or N sites, then the participant was counted as having had an event of interest.

ITT Population

Posted

Number

Participants

From the date of randomization until progression in the T or N site or death due to any cause, assessed after a median of 30.9 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib

Secondary

Loco-regional Control

Loco-regional control is defined as the time from the date of randomization until progression in the T or N site. Participants who died or had secondary primary malignancies in the head and neck region outside of the T and N site or distant metastasis were not counted as an event and were instead treated as competing risks. Per the TNM staging of tumors: T describes the size of the tumor and whether it has invaded nearby tissue, and N describes regional lymph nodes that are involved. Due to the minimal events reported (data cut-off 30-Sep-2010), valid analysis could not be performed for loco-regional control rate.

ITT Population

Posted

From the date of randomization until progression in the T or N site or death due to any cause, assessed after a median of 30.9 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.

Secondary

Number of Participants With Distant Recurrence of Initial Disease

Participants were analyzed for the occurrence of distant metastasis (spread of a disease from one organ or part to another non-adjacent organ or part) after randomization in the study until data cut-off date 1-Aug-2014. Participants who died or had recurrence of disease in the T or N sites or secondary primary malignancies in the head and neck region outside of the original T and N site were not counted as an event and were instead treated as competing risks.

ITT Population

Posted

Number

Participants

From the date of randomization until the first occurrence of distant metastasis, assessed after a median of 30.9 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib

Secondary

Distant Relapse

Distant relapse is defined as the time from the date of randomization until the first occurrence of distant metastasis (spread of a disease from one organ or part to another non-adjacent organ of part). Participants who died or had recurrence of disease in the T or N sites or secondary primary malignancies in the head and neck region outside of the original T and N site were not counted as an event and were instead treated as competing risks.

ITT Population. If a participant had a distant metastasis and then died, then the participant was counted as having had an event of interest.

Posted

Median

Inter-Quartile Range

Months

From the date of randomization until the first occurrence of distant metastasis, assessed after a median of 30.9 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001

Secondary

Number of Participants With Overall Response (OR), as Assessed by the Investigator

Participants with OR were those who achieved either a CR or partial response (PR) from the assessment of overall tumor response at 6 months (24 weeks) following completion of CRT (data cut-off 30-Sep-2010). Per RECIST, CR is defined as the disappearance of all target and non-target lesions; PR is defined as at least a 30% decrease in the sum of the long diameter (LD) of target lesions, taking as a reference, the baseline sum LD. Data are based on Week 24 scans from participants receiving study treatment at that time point.

ITT Population

Posted

Number

Participants

From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001

Secondary

Number of Participants Positive and Negative for the Expression of Biomarkers in Tumor Tissue: Human Epidermal Growth Factor Receptor (HER)-1, HER2, HER3, HER4, P16, and Transforming Growth Factor (TGF-alpha)

Paraffin-embedded tissue block (or sections) from archived tumor tissue sample, if available (from time of original diagnosis) or fresh tumor tissue, was sent for testing to determine intra-tumoral biomarker expression by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) assay. Stained tumor slides or tissue micro arrays (TMAs) were scored by a pathologist from 0 (no expression) to 3+ (high expression). An expression level of >=2+ was considered positive.

ITT Population. Only those participants who had sufficient tumor sample for testing were analyzed.

Posted

Number

Participants

Up to 28 days prior to the date of the first dose of lapatinib/placebo start

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.

Secondary

Plasma Proteome Analysis

Proteomic analyses of blood plasma samples were to be conducted to identify any changes in the proteome profile that could be related to the treatment response. Examination of pre-dosing (screening) plasma protein profiles could uncover novel blood-borne protein candidate biomarkers/profiles, which could be used to predict drug response.

ITT Population. Plasma proteome data have not been analyzed (tested); thus, data are not available to disclose. Based on the negative outcome of Study EGF102988 (NCT00424255), no suitable analyses have been proposed for this small sample size.

Posted

From up to 28 days prior to the first dose of lapatinib/placebo start to 8 weeks after the first dose

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib

Secondary

Analysis of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) From Tumor Samples

No analysis was performed for tumor sample RNA/DNA.

ITT Population. DNA/RNA from tumors has not been analyzed (tested); therefore, data are not available. No suitable analyses of DNA/RNA have been proposed for this small sample size of tumor samples.

Posted

Screening

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.

Secondary

Number of Participants Negative and Positive for Human Papilloma Virus (HPV) Infection, as Determined From Tumor Samples

Analysis was performed for HPV infection analysis from the tumor biopsy samples obtained during the Screening period. p16 was used as a marker for HPV; thus, "negative" participants did not have the p16 marker.

ITT Population

Posted

Number

Participants

Up to 28 days prior to the first dose of lapatinib/placebo

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.

Secondary

Number of Participants Positive and Negative for Biomarker HER1/ErbB1 Categorized in the Indicated Independent Review Panel-assessed Tumor Responses by Expression of Biomarkers From Tumor Tissue: Sensitivity Analysis - 0 Versus (1, 2, 3)

Tumor tissue (fresh or archived) was sent to a central laboratory for biomarker HER1/ErbB1 and tumor genetics analysis up to 1 week after randomization. Per RECIST: CR, disappearance of all lesions; PR, a >=30% decrease in the sum of the longest dimensions (LD) of the target lesions (TLs) taking as a reference the baseline sum LD; Progressive disease (PD), a >=20% increase in the sum of the LD of TLs, or the appearance of >=1 new lesion; Stable Disease (SD), neither PR nor PD, persistence of >=1 non-TL. 0=negative; 1, 2, 3=positive (increasing level of biomarker expression).

ITT Population. Participants assessed for HER1/ ErbB1 expression were analyzed.

Posted

Number

Participants

From the date of randomization until 6 months post chemoradiation treatment, assessed for up to 24 weeks

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.

Secondary

ITT Population. Participants assessed for HER1/ ErbB1 expression were analyzed.

Posted

Number

Participants

From the date of randomization until 6 months post chemoradiation treatment, assessed for up to 24 weeks

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.

Other Pre-specified

Number of Participants Classified as Responders, as Per Volumetric Tumor Response

No analysis was not performed.

ITT Population. A formal analysis of this outcome measure was never performed; thus data are not available and cannot be reported.

Posted

From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months

ID	Title	Description
OG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
OG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0012 affected35 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0013 affected35 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0012 affected35 at risk
Mucosal Inflammation	General disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0013 affected35 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0011 affected35 at risk
Diarrhea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0013 affected35 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0012 affected35 at risk
Hemorrhage	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0011 affected35 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0011 affected35 at risk
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0011 affected35 at risk
Renal Tubular Disorder	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Tumor Hemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Weight Decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Arterial Occlusive Disease	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Creatinine Renal Clearance Decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Death	General disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Ejection Fraction Decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Gastrointestinal Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Gastrostomy Failure	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Hyperuricemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Left Ventricular Dysfunction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Localised Edema	General disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Lung Disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Metastatic Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Mouth Hemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Myocardial Infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Obstructive Airways Disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Parotid Gland Inflammation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Parotitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Pericardial Effusion	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Pharyngeal Ulceration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Quadriparesis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Renal Failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Renal Failure Acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Septic Shock	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Soft Tissue Inflammation	General disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Staphylococcal Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0010 affected35 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Hemiparesis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Hypoaesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Squamous cell carcinoma of the tongue	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0011 affected35 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00017 affected31 at risk EG00122 affected35 at risk
Mucosal Inflammation	General disorders	MedDRA	Systematic Assessment	EG00014 affected31 at risk EG00114 affected35 at risk
Dry Mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00013 affected31 at risk EG00115 affected35 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected31 at risk EG00114 affected35 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00013 affected31 at risk EG0019 affected35 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00013 affected31 at risk EG0017 affected35 at risk
Weight Decreased	Investigations	MedDRA	Systematic Assessment	EG00012 affected31 at risk EG00111 affected35 at risk
Anemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00011 affected31 at risk EG0019 affected35 at risk
Diarrhea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG00118 affected35 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00011 affected31 at risk EG00110 affected35 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG00014 affected31 at risk EG0014 affected35 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0007 affected31 at risk EG00111 affected35 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0006 affected31 at risk EG00111 affected35 at risk
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected31 at risk EG0017 affected35 at risk
Oral Pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0008 affected31 at risk EG0017 affected35 at risk
Radiation Skin Injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0009 affected31 at risk EG0015 affected35 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0008 affected31 at risk EG0015 affected35 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0007 affected31 at risk EG0015 affected35 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0008 affected31 at risk EG00117 affected35 at risk
Skin Reaction	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0005 affected31 at risk EG0018 affected35 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0006 affected31 at risk EG0016 affected35 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected31 at risk EG0015 affected35 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected31 at risk EG0015 affected35 at risk
Hemoglobin Decreased	Investigations	MedDRA	Systematic Assessment	EG0007 affected31 at risk EG0017 affected35 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0017 affected35 at risk
Localized Edema	General disorders	MedDRA	Systematic Assessment	EG0007 affected31 at risk EG0014 affected35 at risk
Creatinine Renal Clearance Decreased	Investigations	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0016 affected35 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0006 affected31 at risk EG0014 affected35 at risk
Neck Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0006 affected31 at risk EG0014 affected35 at risk
Oral Candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected31 at risk EG0014 affected35 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0015 affected35 at risk
Blood Creatinine Increased	Investigations	MedDRA	Systematic Assessment	EG0008 affected31 at risk EG0012 affected35 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0005 affected31 at risk EG0014 affected35 at risk
Radiation Mucositis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0005 affected31 at risk EG0014 affected35 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0016 affected35 at risk
Aspartate Aminotransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0007 affected31 at risk EG0011 affected35 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0014 affected35 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0016 affected35 at risk
Oral Fungal Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected31 at risk EG0013 affected35 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0014 affected35 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0014 affected35 at risk
Ear Pain	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0012 affected35 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0014 affected35 at risk
Pain	General disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0013 affected35 at risk
Blood Bilirubin Increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0012 affected35 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0013 affected35 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0012 affected35 at risk
Gastroesophageal Reflux Disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0012 affected35 at risk
Laryngeal Edema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0013 affected35 at risk
Edema Peripheral	General disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0012 affected35 at risk
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0013 affected35 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0013 affected35 at risk
Renal Failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0011 affected35 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0011 affected35 at risk
Aptyalism	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0011 affected35 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0013 affected35 at risk
Epiglottic Edema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected31 at risk EG0010 affected35 at risk
Hemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0012 affected35 at risk
Increased Upper Airway Secretion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0011 affected35 at risk
Increased Viscosity of Bronchial Secretion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0012 affected35 at risk
Mouth Ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0013 affected35 at risk
Oral Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0012 affected35 at risk
Salivary Gland Disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0012 affected35 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0011 affected35 at risk
Aphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Blood Sodium Decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Blood Urea Increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Cheilitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Chills	General disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0010 affected35 at risk
Depressed Mood	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk
Face Edema	General disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0013 affected35 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Neutrophil Count Increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0012 affected35 at risk
Procedural Pain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0003 affected31 at risk EG0010 affected35 at risk
Productive Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Tongue Ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0013 affected35 at risk
Aphonia	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Aplasia	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Catheter Site Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Ejection Fraction Decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Fibrosis	General disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Gamma Glutamyltransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Glossitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Gout	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Influenza Like Illness	General disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Lethargy	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Nail Disorder	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Proctalgia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0010 affected35 at risk
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Conjunctivitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Dental caries	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Fungal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk
Oral mucosal erythema	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected31 at risk EG0012 affected35 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected31 at risk EG0012 affected35 at risk
White blood cell count decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected31 at risk EG0011 affected35 at risk

ID	Term
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D013812	Therapeutics

ID	Title	Description
BG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
BG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Chemoradiotherapy + Placebo, Followed by Placebo	Participants received radiotherapy once daily (OD), with a dose/fraction less than 2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.			18	31	31	31
EG001	Chemoradiotherapy + Lapatinib, Followed by Lapatinib	Participants received radiotherapy once daily (OD), with a dose/fraction less than 2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.			22	35	34	35