Study Of Adjuvant Lapatinib In High-Risk Head And Neck Ca... | NCT00424255

Label	Type	Description	Intervention Names
Lapatinib+Chemoradiation	Experimental	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
Placebo+Chemoradiation	Placebo Comparator	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 Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Lapatinib	Drug	Dual ErbB1/2 inhibitor	Lapatinib+Chemoradiation
Chemoradiation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Disease Free Survival (DFS)	DFS is defined as the time from randomization until the earliest date of disease recurrence (evidence of local, regional, or distant disease progression, second primary tumor) or death due to any cause. Disease recurrence was based on the assessments from the blinded, independent reviewer (radiological and clinical). Participants who initiated alternative anti-cancer therapy prior to disease recurrence or death were treated as censored at the last assessment prior to the time of this initiation. For participants whose disease did not recur or who did not die, DFS was censored at the time of the last independently assessed radiological scan (where initiation of alternative anti-cancer therapy had not commenced). Participants who missed two or more consecutive disease assessments were censored at the last assessment prior to the missed assessments. Participants considered to have malignant disease at Baseline were censored at the time of randomization.	From randomization until the earliest date of disease recurrence or death due to any cause (average of 101 study weeks)

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization until death due to any cause. For participants who did not die, the time to death was censored at the time of last visit/contact.	From randomization until death due to any cause (average of 131 study weeks)
Disease Specific Survival (DSS)

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Springfield	Illinois	62794	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
39415507	Derived	Sunkara PR, Chow E, Waitzman J, Sukari A, Cramer JD. The Prognostication of Surgically Resected Head and Neck Squamous Cell Carcinoma Using Pre-Therapy Neutrophil and Lymphocyte Counts. Head Neck. 2025 Feb;47(2):687-694. doi: 10.1002/hed.27949. Epub 2024 Oct 16.
36821132	Derived	Sunkara PR, Graff JT, Cramer JD. Association of Surgical Margin Distance With Survival in Patients With Resected Head and Neck Squamous Cell Carcinoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2023 Apr 1;149(4):317-326. doi: 10.1001/jamaoto.2022.5186.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
BG001	Lapatinib 1500 mg	Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
BG002	Total	Total of all reporting groups

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

Disease Free Survival (DFS)

DFS is defined as the time from randomization until the earliest date of disease recurrence (evidence of local, regional, or distant disease progression, second primary tumor) or death due to any cause. Disease recurrence was based on the assessments from the blinded, independent reviewer (radiological and clinical). Participants who initiated alternative anti-cancer therapy prior to disease recurrence or death were treated as censored at the last assessment prior to the time of this initiation. For participants whose disease did not recur or who did not die, DFS was censored at the time of the last independently assessed radiological scan (where initiation of alternative anti-cancer therapy had not commenced). Participants who missed two or more consecutive disease assessments were censored at the last assessment prior to the missed assessments. Participants considered to have malignant disease at Baseline were censored at the time of randomization.

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

Posted

Median

95% Confidence Interval

Months

From randomization until the earliest date of disease recurrence or death due to any cause (average of 101 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001	Lapatinib 1500 mg	Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Units	Counts
Participants	OG000342 OG001346

Title

Denominators

Categories

Title	Measurements
	OG000NA(54.6 to NA)Because of an insufficient number of events, the median and the upper limit of the confidence interval were not reached. OG00153.6(45.8 to NA)Because of an insufficient number of events, the upper limit of the confidence interval was not reached.

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		Non-stratified log-rank test		0.2251	The one-sided p-value is unstratified as there are too few events per stratum to perform a stratified test.						95						No	Superiority or Other
OG000 OG001		Non-stratified log-rank test

Secondary

Overall Survival (OS)

OS is defined as the time from randomization until death due to any cause. For participants who did not die, the time to death was censored at the time of last visit/contact.

ITT Population

Posted

Median

95% Confidence Interval

Months

From randomization until death due to any cause (average of 131 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001	Lapatinib 1500 mg	Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

Disease Specific Survival (DSS)

DSS is defined as the time from randomization until death due to head and neck cancer. Participants whose death was not related to the disease under study were treated as competing risks at the time death occured. Participants who were alive were censored at the time of their last visit.

ITT Population

Posted

Median

95% Confidence Interval

Months

From randomization until death due to head and neck cancer (average of 131 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001	Lapatinib 1500 mg	Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

Time to Locoregional Recurrence (TTLR)

TTLR is defined as the time from randomization until the first occurrence that local and/or regional recurrence is documented or the date of censor. Local relapse is defined as recurrent cancer in the primary tumor bed not clearly attributable to a second primary neoplasm. Regional relapse is defined as recurrent cancer in the neck not clearly attributable to a second primary neoplasm. All other events prior to locoregional recurrence were treated as competing risks at the time they occured. All other participants were treated as censored at the time of their last disease assessment. Participants with malignant disease at Baseline according to the independent review were censored at the time of randomization for the analysis of independently reviewed data.

ITT Population

Posted

Median

95% Confidence Interval

Months

From randomization until thefirst occurrence that local and/or regional recurrence is documented or the date of censor (average of 101 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

Time to Distant Relapse (TTDR)

TTDR is defined as the time from randomization until the first occurrence that distant relapse is documented. Distant relapse is defined as clear evidence of distant metastases (lung, bone, brain, etc.). Metastasis is defined as the spread of a cancer from one organ or part to another non-adjacent organ or part. All other events prior to a distant relapse were treated as competing risks at the time they occured. All other participants were treated as censored at the time of their last disease assessment. Participants with malignant disease at Baseline according to the independent review were censored at the time of randomization for the analysis of independently reviewed data.

ITT Population

Posted

Median

95% Confidence Interval

Months

From randomization until the first documented occurrence that distant relapse is documented (average of 101 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001

Secondary

Number of Participants With a Second Primary Tumor

Participants who developed a second primary tumor at the time of the first recurrence or within 28 days of the first recurrence were measured. The criteria for a second primary tumor are as follows: a distinct lesion separated from the primary tumor site by >2 centimeters of normal epithelium; or a new cancer with different histology; or any cancer, regardless of site, occurring >=3 years after initial treatment. Participants with baseline disease were included in the denominator when calculating the percentage.

ITT Population

Posted

Number

Participants

From randomization until development of second primary tumor or within 28 days of first recurrence (average of 101 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001	Lapatinib 1500 mg

Secondary

Extent of Exposure

Extent of exposure is defined as the duration of treatment administered during the study. The mean duration of treatment is calculated as the number of days between the start of treatment and the end of treatment inclusive (i.e., treatment stop date minus treatment start date + 1). Participants were counted in a treatment phase (monotherapy, chemoradiotherapy, and maintenance) if they had received any dose in that phase. Participants randomized to placebo who received >=1 dose of lapatinib in error were included in the lapatinib arm.

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.

Posted

Mean

Standard Deviation

Weeks

From randomization until end of 1year maintenance treatment (average of 63 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of non-serious AEs occurring at a frequency threshold of 5% and SAEs.

Safety Population

Posted

Number

Participants

From the first dose of lapatinib/placebo until 5 days after the last dose (average of 141 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

Data are summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI CTC version 3.0) toxicity grades. Data are reported as the number of participants who had a grade 3 (G3) or grade 4 (G4) toxicity for the indicated chemistry parameters, where G3 indicates a severe toxicity and G4 indicates a life-threatening toxicity. Clinical chemistry parameters included: albumin, alkaline phosphatase (AP), alanine amino transferase (ALT), aspartate amino transeferase (AST), total bilirubin (TB), calcium, carbon dioxide content/bicarbonate (CO2/HCO3), creatinine, glucose, potassium, and sodium. The worst-case on-therapy visit includes any scheduled or unscheduled post-Baseline visit.

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.

Posted

Number

Participants

From Baseline (within 8 weeks prior to randomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

Data are summarized using the NCI CTC version 3.0 toxicity grades. Data are reported as the number of participants who had a grade 3 (G3) or grade 4 (G4) toxicity for the indicated hematological parameters, where G3 indicates a severe toxicity and G4 indicates a life-threatening toxicity. The worst-case on-therapy visit includes any scheduled or unscheduled post-Baseline visit. Hematology parameter included: hemoglobin, total neutrophils (TN), platelet count (PC), and White Blood Cell (WBC) count.

Posted

Number

Participants

From Baseline (within 8 weeks prior torandomization [Day 1]) until the end of the maintenance period/early withdrawal (up to Study Week 64)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

Late radiation morbidity event data are summarized as the number of participants with late radiation morbidity events per system organ class (SOC). Late radiation effects are defined as those that first occur 90 days or more after the initiation of radiation therapy.

Safety Population

Posted

Number

Participants

From 180 days after completion of radiation until the last follow-up/withdrawal visit (average of 64 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001	Lapatinib 1500 mg	Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

Change From Baseline in Blood Pressure at the Indicated Time Points

Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Posted

Mean

Standard Deviation

Millimeters of mercury (mmHg)

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)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

Change From Baseline in Heart Rate at the Indicated Time Points

Heart rate (HR) was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Posted

Mean

Standard Deviation

Beats per minute

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)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001

Secondary

Change From Baseline in Body Temperature at the Indicated Time Points

Body temperature was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Posted

Mean

Standard Deviation

Degrees Centigrade

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)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001

Secondary

Change From Baseline in Body Weight at the Indicated Time Points

Body weight was measured at Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, End of CRT, MW 8, MW 16, MW 24, MW 32, MW 40, MW 48, MW 56, and at the time of withdrawal from IP. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Posted

Mean

Standard Deviation

Kilograms

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)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001

Secondary

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

A 12-lead ECG was recorded at Baseline, at the end of the CRT, at Maintenance Week 56, at withdrawal from IP, and at anytime post-baseline. Data are presented as clinically significant (CS) or not clinically significant (NCS) abnormal findings. The study investigator determined if an abnormal ECG finding was CS or NCS.

Posted

Number

Participants

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)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

The Eastern Cooperative Oncology Group (ECOG) performance status scales and grades/criteria are used by doctors and researchers to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead.

Safety Population

Posted

Number

Participants

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)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

Change from Baseline in quality of life status was assessed using the FACT-H&N questionnaire, which is designed to measure multidimensional quality of life in participants with head and neck cancer. Change from Baseline was analyzed using parametric analysis of covariance (with the Baseline value as a covariate). The FACT-H&N questionnaire contains 39 items (27 general questions and 12 head and neck cancer-specific items) covering 4 dimensions and 1 subscale: physical well-being, social/family well-being, emotional well-being, functional well-being, and a head and neck cancer subscale. Possible subscale scores range from 0 to 36. Higher scores represent better quality of life. Data were adjusted for participant-reported quality of life scores at Baseline.

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

Posted

Least Squares Mean

Standard Error

scores on a scale

From randomization until the last follow-up/withdrawal visit (up to 62 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

Change from Baseline in quality of life status was assessed using the EQ-5D scale, a 5-item health status measure and a visual analog rating scale. Change from Baseline was analyzed using parametric analysis of covariance (with the Baseline value as a covariate). The EQ-5D is a generic measure of self-reported health outcomes that is applicable to a wide range of health conditions and treatments. The EQ-5D covers health status in 5 domains (3 questions each): mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each item is scored as follows: 1, no problems; 2, some moderate problems; 3, extreme problems. The possible EQ-5D index utility values range from 0.594 to 1, and the thermometer score ranges from 0 to 100. Higher scores represent better quality of life. Data were adjusted for participant-reported quality of life scores at Baseline.

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

Posted

Least Squares Mean

Standard Error

scores on a scale

From randomization until the last follow-up/withdrawal visit (up to 62 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

Number of Participants With the Indicated Biomarker Expression Status

Biomarkers (which influence clinical response) assessed from tumor tissues included P16, Human Papilloma virus (HPV), and Epidermal Growth Factor Receptor (EGFR)/Epidermal Growth Factor Receptor 1 (ErbB1). Biomarker expression is presented as positive, negative, or unknown. Participants in the ErbB1-positive category include those with results of positive or strongly positive.

ITT Population

Posted

Number

Participants

Baseline (BL; within 8 weeks prior to randomization [Day 1]) (up to Study Week 1)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.
OG001	Lapatinib 1500 mg	Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Secondary

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

LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart with each contraction. LVEF was assessed using echocardiogram (ECHO: a test of the action of the heart using ultrasound waves to produce a visual display, for the diagnosis or monitoring of heart disease ) and multigated acqusition scans (MUGA scan: a noninvasive diagnostic test used to evaluate the pumping function of the ventricles). Data from the ECHO and MUGA scans were combined, and the absolute change from Baseline (Abs) data are presented according to the following categories: No change or any increase, 0-<10% decrease, 10-19% decrease, >=20% decrease, >=10% decrease and >=the Lower Limit of Normal (LLN), >=10% decrease and below LLN, >=20% decrease and >=LLN, or >=20% decrease and below LLN. The relative percent change from Baseline (Rel) data are presented according to the following categories: >=20% decrease and >=LLN and >=20% decrease and below LLN.

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

Posted

Number

Participants

From the end of the CRT until the last follow-up visit (average of 141 study weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo per oral monotherapy once daily (QD) for 1 week, followed by radiotherapy of 2 Gray (Gy) per day for 5 days per week (for a total dose of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 milligrams per meters squared (mg/m^2) intravenously (IV) on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received placebo per oral administration QD, followed by maintenance placebo per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.			133	336	321	336
EG001	Lapatinib 1500 mg	Participants received lapatinib 1500 mg per oral monotherapy QD for 1 week, followed by radiotherapy of 2 Gy per day for 5 days per week (for a total of 66 Gy for up to 7 weeks). Participants received concurrent cisplatin 100 mg/m^2 IV on Days 1, 22, and 43 of radiotherapy. One week prior to the start of chemoradiotherapy, then concurrently for 6 to approximately 7 weeks with chemoradiotherapy, participants received lapatinib 1500 mg per oral administration QD, followed by maintenance lapatinib 1500 mg per oral monotherapy QD for up to 1 year or until evidence of disease relapse, whichever was sooner.			169	349	337	349

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00017 affected336 at risk EG00118 affected349 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00010 affected336 at risk EG00110 affected349 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0017 affected349 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0004 affected336 at risk EG0015 affected349 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0005 affected336 at risk EG0014 affected349 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0012 affected349 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Haematotoxicity	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Mucosal inflammation	General disorders	MedDRA	Systematic Assessment	EG0009 affected336 at risk EG00117 affected349 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0005 affected336 at risk EG0016 affected349 at risk
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0006 affected336 at risk EG0014 affected349 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0014 affected349 at risk
Death	General disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0014 affected349 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0012 affected349 at risk
Impaired healing	General disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Malaise	General disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0010 affected349 at risk
Medical device complication	General disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Catheter site discharge	General disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Catheter site related reaction	General disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Disease progression	General disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Face oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Mucosal induration	General disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Performance status decreased	General disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Sudden death	General disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0008 affected336 at risk EG00112 affected349 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected336 at risk EG00111 affected349 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0017 affected349 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0016 affected349 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected336 at risk EG0014 affected349 at risk
Oesophageal stenosis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0013 affected349 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0012 affected349 at risk
Oral pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Anal fistula	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Gastrooesophagitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Haematemesis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Oesophageal fistula	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Oesophagitis ulcerative	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Retroperitoneal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Stomatitis haemorrhagic	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0006 affected336 at risk EG00112 affected349 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0005 affected336 at risk EG0016 affected349 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected336 at risk EG0013 affected349 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0015 affected349 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0013 affected349 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0014 affected349 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0011 affected349 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0011 affected349 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0013 affected349 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0013 affected349 at risk
Feeding disorder	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0012 affected349 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Metabolic disorder	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected336 at risk EG0016 affected349 at risk
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0014 affected349 at risk
Wound infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0013 affected349 at risk
Bronchopneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Erysipelas	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0010 affected349 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Lung abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0012 affected349 at risk
Lung infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Neutropenic sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Oral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0012 affected349 at risk
Abscess limb	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Abscess neck	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Bacteraemia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Blister infected	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Catheter site infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Febrile infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Lobar pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Osteomyelitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Otitis media	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Paraoesophageal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Parotid abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Perichondritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Sepsis syndrome	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Septic shock	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Streptococcal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Superinfection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Tooth abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Tooth infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Tracheitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Ejection fraction decreased	Investigations	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG00110 affected349 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0015 affected349 at risk
Hepatic enzyme increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0013 affected349 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0014 affected349 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0011 affected349 at risk
Blood uric acid increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0012 affected349 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0010 affected349 at risk
Glomerular filtration rate decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Alanine aminotransferase abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Blood bilirubin abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Calcium ionised decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Electrocardiogram abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Electrocardiogram change	Investigations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0012 affected349 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0013 affected349 at risk
Pharyngeal fistula	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0012 affected349 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0012 affected349 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0011 affected349 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0010 affected349 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0012 affected349 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Laryngeal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0010 affected349 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Laryngeal disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Pharyngeal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Osteoradionecrosis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0006 affected336 at risk EG0011 affected349 at risk
Tracheostomy malfunction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0013 affected349 at risk
Radiation mucositis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0012 affected349 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Anastomotic stenosis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Feeding tube complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Foreign body	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Implant tissue necrosis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Radiation sickness syndrome	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Traumatic fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Wound complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0011 affected349 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0012 affected349 at risk
Ataxia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Brain hypoxia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Brain injury	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Cerebral infarction	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Dyskinesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Grand mal convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Paralysis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0012 affected349 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0010 affected349 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Temporomandibular joint syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Cardiac arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0011 affected349 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0012 affected349 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Cardiac failure acute	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Diastolic dysfunction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Intracardiac mass	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Ventricular hypokinesia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Bronchial carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Neoplasm recurrence	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Oesophageal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Oral fibroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Second primary malignancy	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0014 affected349 at risk
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0010 affected349 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Pemphigus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Haematoma	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0002 affected336 at risk EG0010 affected349 at risk
Arterial rupture	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Arterial thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Deep vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Femoral artery occlusion	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Haemorrhage	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Venous thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Venous thrombosis limb	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Renal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0013 affected349 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0003 affected336 at risk EG0010 affected349 at risk
Renal impairment	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0012 affected349 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0012 affected349 at risk
Completed suicide	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Suicide attempt	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0012 affected349 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Neurosensory hypoacusis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Aplasia	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Hypothyroidism	Endocrine disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0010 affected349 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Periorbital oedema	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Hepatitis E	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected336 at risk EG0011 affected349 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Oral neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Squamous cell carcinoma of the oral cavity	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk
Testis cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected336 at risk EG0011 affected349 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG00031 affected336 at risk EG00130 affected349 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG00028 affected336 at risk EG00133 affected349 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG00033 affected336 at risk EG00144 affected349 at risk
Creatinine renal clearance decreased	Investigations	MedDRA	Systematic Assessment	EG00017 affected336 at risk EG00127 affected349 at risk
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG00029 affected336 at risk EG00133 affected349 at risk
Lymphocyte count decreased	Investigations	MedDRA	Systematic Assessment	EG00018 affected336 at risk EG00120 affected349 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG00064 affected336 at risk EG00190 affected349 at risk
White blood cell count decreased	Investigations	MedDRA	Systematic Assessment	EG00023 affected336 at risk EG00130 affected349 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00061 affected336 at risk EG00177 affected349 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00099 affected336 at risk EG00183 affected349 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00075 affected336 at risk EG00187 affected349 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00077 affected336 at risk EG00170 affected349 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00025 affected336 at risk EG00124 affected349 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG00045 affected336 at risk EG00159 affected349 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00036 affected336 at risk EG00141 affected349 at risk
Mucosal inflammation	General disorders	MedDRA	Systematic Assessment	EG000208 affected336 at risk EG001220 affected349 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG00060 affected336 at risk EG00163 affected349 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00074 affected336 at risk EG00160 affected349 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00041 affected336 at risk EG001147 affected349 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG000131 affected336 at risk EG001148 affected349 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00021 affected336 at risk EG00130 affected349 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG000113 affected336 at risk EG001125 affected349 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG000150 affected336 at risk EG001181 affected349 at risk
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00034 affected336 at risk EG00141 affected349 at risk
Oral pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00035 affected336 at risk EG00125 affected349 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00050 affected336 at risk EG00150 affected349 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG000115 affected336 at risk EG001154 affected349 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00037 affected336 at risk EG00145 affected349 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00021 affected336 at risk EG00123 affected349 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00067 affected336 at risk EG00145 affected349 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00036 affected336 at risk EG00125 affected349 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00069 affected336 at risk EG00162 affected349 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00028 affected336 at risk EG00142 affected349 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00025 affected336 at risk EG00133 affected349 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG00045 affected336 at risk EG00131 affected349 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00028 affected336 at risk EG00120 affected349 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG00020 affected336 at risk EG00117 affected349 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00023 affected336 at risk EG00115 affected349 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00028 affected336 at risk EG00120 affected349 at risk
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG00022 affected336 at risk EG00117 affected349 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0009 affected336 at risk EG00123 affected349 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG000101 affected336 at risk EG001167 affected349 at risk
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00037 affected336 at risk EG00141 affected349 at risk
Radiation mucositis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG00019 affected336 at risk EG00113 affected349 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG00079 affected336 at risk EG00155 affected349 at risk

ID	Term
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003131	Combined Modality Therapy
D013812	Therapeutics
D004358	Drug Therapy
D011878	Radiotherapy