BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cel... | NCT00656136

ID	Type	Description	Link
2007-005983-28	EudraCT Number	EudraCT

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Patients receive placebo once daily	Drug: placebo
BIBW 2992	Experimental	Patients receive BIBW 2992 tablets once daily	Drug: BIBW 2992

Name	Type	Description	Arm Group Labels	Other Names
placebo	Drug	Patients receive placebo once daily	Placebo
BIBW 2992

Measure	Description	Time Frame
Overall Survival	Overall survival was the duration from the date of randomization to the date of death. Patients who were alive were censored at the last contact date prior to the database lock. For the primary analysis 11 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Primary analysis data cut-off date was 08 July 2010. For the final analysis 13 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Final analysis data cut-off date was 04 October 2013.	From randomization until death or the last patient out date, an average of 12 months

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST 1.0).	From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1200.23.038 Boehringer Ingelheim Investigational Site		Kingman	Arizona		United States
1200.23.046 Boehringer Ingelheim Investigational Site

PubMed Identifier	Type	Citation	Retractions
22452896	Derived	Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. doi: 10.1016/S1470-2045(12)70087-6. Epub 2012 Mar 26.

ID	Title	Description
FG000	Placebo Plus Best Supportive Care (BSC)	Patients received matching placebo for 50 mg, 40 mg or 30 mg afatinib tablets starting with 50 mg/day. Dose reductions were managed in the same way as for the afatinib arm.
FG001	Afatinib 50 mg/Day Plus Best Supportive Care (BSC)

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

Overall Survival

Overall survival was the duration from the date of randomization to the date of death. Patients who were alive were censored at the last contact date prior to the database lock.

For the primary analysis 11 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Primary analysis data cut-off date was 08 July 2010.

For the final analysis 13 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Final analysis data cut-off date was 04 October 2013.

Randomized set was all patients who were randomized and for this study all of these patients received at least one dose of study medication.

Posted

Median

95% Confidence Interval

Months

From randomization until death or the last patient out date, an average of 12 months

ID	Title	Description
OG000	Placebo Plus Best Supportive Care (BSC)	Patients received matching placebo for 50 mg, 40 mg or 30 mg afatinib tablets starting with 50 mg/day. Dose reductions were managed in the same way as for the afatinib arm.
OG001	Afatinib 50 mg/Day Plus Best Supportive Care (BSC)	Patients started with a 50 mg/day dose. Dose reductions were permitted by the protocol to 40 mg/day plus BSC or 30 mg /day plus BSC based upon prespecified Adverse Events and Common Terminology Criteria for Adverse Events (CTCAE) grade (Version 3.0).

Units	Counts
Participants	OG000195 OG001390

Title

Denominators

Categories

Primary analysis (358 deaths)

Title	Measurements
	OG00011.96(10.15 to 14.26) OG00110.78(9.95 to 11.99)

Final analysis (526 deaths)

Title	Measurements
	OG000

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	Primary analysis was performed after 358 deaths were observed among randomized patients. The data cut-off date for the primary analysis was 08 July 2010.	Regression, Cox	Model stratified by gender and baseline ECOG score (0,1 vs 2)	0.7428	P-value is one-sided (afatinib vs placebo) log rank test stratified by gender and baseline ECOG score (0,1 vs 2)	Hazard Ratio (HR)	1.077			2-Sided	95	0.862	1.346				No	Superiority or Other

Secondary

Progression-free Survival (PFS)

PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST 1.0).

Randomized set was all patients who were randomized and for this study all of these patients received at least one dose of study medication.

Posted

Median

95% Confidence Interval

Months

From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months

ID	Title	Description
OG000	Placebo Plus Best Supportive Care (BSC)	Patients received matching placebo for 50 mg, 40 mg or 30 mg afatinib tablets starting with 50 mg/day. Dose reductions were managed in the same way as for the afatinib arm.
OG001	Afatinib 50 mg/Day Plus Best Supportive Care (BSC)	Patients started with a 50 mg/day dose. Dose reductions were permitted by the protocol to 40 mg/day plus BSC or 30 mg /day plus BSC based upon prespecified Adverse Events and Common Terminology Criteria for Adverse Events (CTCAE) grade (Version 3.0).

Units	Counts

Secondary

Objective Response Rate (OR)

OR is defined as complete response (CR) and partial response (PR). Assessed by central independent review according to RECIST 1.0.

Randomized set was all patients who were randomized and for this study all of these patients received at least one dose of study medication.

Posted

Number

95% Confidence Interval

Percentage of patients with OR

From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months

ID	Title	Description
OG000	Placebo Plus Best Supportive Care (BSC)	Patients received matching placebo for 50 mg, 40 mg or 30 mg afatinib tablets starting with 50 mg/day. Dose reductions were managed in the same way as for the afatinib arm.
OG001	Afatinib 50 mg/Day Plus Best Supportive Care (BSC)	Patients started with a 50 mg/day dose. Dose reductions were permitted by the protocol to 40 mg/day plus BSC or 30 mg /day plus BSC based upon prespecified Adverse Events and Common Terminology Criteria for Adverse Events (CTCAE) grade (Version 3.0).

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Disseminated intravascular coagulation	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Febrile neutropenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Lymphadenopathy	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Neutropenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Acute left ventricular failure	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Atrial fibrillation	Cardiac disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0011 affected390 at risk
Cardiac failure	Cardiac disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0012 affected390 at risk
Cardiac tamponade	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Cardio-respiratory arrest	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Myocardial infarction	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Pericardial effusion	Cardiac disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0012 affected390 at risk
Sick sinus syndrome	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Supraventricular tachycardia	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Tachycardia	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Blindness	Eye disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Diplopia	Eye disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Eye movement disorder	Eye disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Vision blurred	Eye disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Abdominal discomfort	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Abdominal pain	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Abdominal pain upper	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Ascites	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Diarrhoea	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG00118 affected390 at risk
Dysphagia	Gastrointestinal disorders	16.1	Systematic Assessment	EG0003 affected195 at risk EG0010 affected390 at risk
Haematemesis	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Ileus	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Intestinal obstruction	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Nausea	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0014 affected390 at risk
Pancreatitis	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Pancreatitis acute	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0014 affected390 at risk
Proctalgia	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Rectal haemorrhage	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Stomatitis	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0013 affected390 at risk
Vomiting	Gastrointestinal disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0015 affected390 at risk
Asthenia	General disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0011 affected390 at risk
Chest discomfort	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Chest pain	General disorders	16.1	Systematic Assessment	EG0002 affected195 at risk EG0010 affected390 at risk
Condition aggravated	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Death	General disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0013 affected390 at risk
Extravasation	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Face oedema	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Fatigue	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0013 affected390 at risk
General physical health deterioration	General disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0012 affected390 at risk
Hernia	General disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Malaise	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Medical device complication	General disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Multi-organ failure	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Oedema peripheral	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Pain	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Pyrexia	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0017 affected390 at risk
Sudden cardiac death	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Sudden death	General disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Acute hepatic failure	Hepatobiliary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Hepatitis acute	Hepatobiliary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Atypical pneumonia	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Bacteraemia	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Candida infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Cellulitis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Device related infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Gastroenteritis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Gastroenteritis viral	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Lower respiratory tract infection fungal	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Lung infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0014 affected390 at risk
Paronychia	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Peritonitis bacterial	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Pneumonia	Infections and infestations	16.1	Systematic Assessment	EG0004 affected195 at risk EG00110 affected390 at risk
Sepsis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Septic shock	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0015 affected390 at risk
Soft tissue infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Upper respiratory tract infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Wound infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Fall	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Head injury	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Humerus fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Multiple fractures	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Blood creatinine increased	Investigations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0014 affected390 at risk
Blood culture positive	Investigations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Blood potassium increased	Investigations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Electrocardiogram T wave inversion	Investigations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Oxygen saturation decreased	Investigations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Prostatic specific antigen increased	Investigations	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Decreased appetite	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0013 affected390 at risk
Dehydration	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0018 affected390 at risk
Hypocalcaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Hypokalaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0015 affected390 at risk
Hyponatraemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Back pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0002 affected195 at risk EG0011 affected390 at risk
Bone pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0012 affected390 at risk
Flank pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0013 affected390 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0011 affected390 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Lung adenocarcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Malignant ascites	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0007 affected195 at risk EG00116 affected390 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0001 affected195 at risk EG0011 affected390 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0003 affected195 at risk EG00111 affected390 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Altered state of consciousness	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Brain mass	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Brain oedema	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Cerebral haemorrhage	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Cerebral infarction	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Cerebrovascular accident	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Convulsion	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Dizziness	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0013 affected390 at risk
Dysarthria	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Embolic cerebral infarction	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Headache	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Hemiparesis	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Hydrocephalus	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Intracranial pressure increased	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Ischaemic stroke	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Paraesthesia	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Paraplegia	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Partial seizures	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Spinal cord compression	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Tremor	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
VIIth nerve paralysis	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0011 affected390 at risk
Delirium	Psychiatric disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Acute prerenal failure	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Oliguria	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Renal colic	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Renal failure	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Renal failure acute	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0017 affected390 at risk
Renal impairment	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Pelvic pain	Reproductive system and breast disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Cough	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0003 affected195 at risk EG0010 affected390 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0004 affected195 at risk EG0018 affected390 at risk
Dyspnoea at rest	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0012 affected390 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0010 affected390 at risk
Hydropneumothorax	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0007 affected195 at risk EG00114 affected390 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0015 affected390 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0002 affected195 at risk EG0019 affected390 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Rash	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Deep vein thrombosis	Vascular disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG0015 affected390 at risk
Hypertensive crisis	Vascular disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0011 affected390 at risk
Hypotension	Vascular disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk
Thrombosis	Vascular disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG0012 affected390 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0003 affected195 at risk EG00123 affected390 at risk
Abdominal pain upper	Gastrointestinal disorders	16.1	Systematic Assessment	EG0008 affected195 at risk EG00125 affected390 at risk
Constipation	Gastrointestinal disorders	16.1	Systematic Assessment	EG00024 affected195 at risk EG00143 affected390 at risk
Diarrhoea	Gastrointestinal disorders	16.1	Systematic Assessment	EG00018 affected195 at risk EG001334 affected390 at risk
Mouth ulceration	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG00151 affected390 at risk
Nausea	Gastrointestinal disorders	16.1	Systematic Assessment	EG00039 affected195 at risk EG00190 affected390 at risk
Stomatitis	Gastrointestinal disorders	16.1	Systematic Assessment	EG0002 affected195 at risk EG00182 affected390 at risk
Vomiting	Gastrointestinal disorders	16.1	Systematic Assessment	EG00025 affected195 at risk EG00175 affected390 at risk
Asthenia	General disorders	16.1	Systematic Assessment	EG00016 affected195 at risk EG00136 affected390 at risk
Chest pain	General disorders	16.1	Systematic Assessment	EG00011 affected195 at risk EG00127 affected390 at risk
Fatigue	General disorders	16.1	Systematic Assessment	EG00023 affected195 at risk EG00172 affected390 at risk
Mucosal inflammation	General disorders	16.1	Systematic Assessment	EG0002 affected195 at risk EG00195 affected390 at risk
Pyrexia	General disorders	16.1	Systematic Assessment	EG0007 affected195 at risk EG00136 affected390 at risk
Folliculitis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected195 at risk EG00125 affected390 at risk
Paronychia	Infections and infestations	16.1	Systematic Assessment	EG0001 affected195 at risk EG001131 affected390 at risk
Weight decreased	Investigations	16.1	Systematic Assessment	EG0002 affected195 at risk EG00137 affected390 at risk
Decreased appetite	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG00022 affected195 at risk EG001118 affected390 at risk
Hypokalaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0004 affected195 at risk EG00129 affected390 at risk
Back pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG00022 affected195 at risk EG00129 affected390 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0003 affected195 at risk EG00120 affected390 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0004 affected195 at risk EG00127 affected390 at risk
Dizziness	Nervous system disorders	16.1	Systematic Assessment	EG0006 affected195 at risk EG00120 affected390 at risk
Dysgeusia	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG00122 affected390 at risk
Headache	Nervous system disorders	16.1	Systematic Assessment	EG0009 affected195 at risk EG00121 affected390 at risk
Insomnia	Psychiatric disorders	16.1	Systematic Assessment	EG00010 affected195 at risk EG00117 affected390 at risk
Cough	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG00036 affected195 at risk EG00154 affected390 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG00022 affected195 at risk EG00154 affected390 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG00173 affected390 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG00013 affected195 at risk EG0019 affected390 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0002 affected195 at risk EG00142 affected390 at risk
Acne	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG00127 affected390 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0001 affected195 at risk EG00128 affected390 at risk
Dry skin	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG00014 affected195 at risk EG00162 affected390 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG00130 affected390 at risk
Pruritus	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG00011 affected195 at risk EG00173 affected390 at risk
Rash	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG00023 affected195 at risk EG001248 affected390 at risk
Skin fissures	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected195 at risk EG00132 affected390 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D000577	Amides
D009930	Organic Chemicals
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Placebo Plus Best Supportive Care (BSC)	Patients received matching placebo for 50 mg, 40 mg or 30 mg afatinib tablets starting with 50 mg/day. Dose reductions were managed in the same way as for the afatinib arm.
BG001	Afatinib 50 mg/Day Plus Best Supportive Care (BSC)	Patients started with a 50 mg/day dose. Dose reductions were permitted by the protocol to 40 mg/day plus BSC or 30 mg /day plus BSC based upon prespecified Adverse Events and Common Terminology Criteria for Adverse Events (CTCAE) grade (Version 3.0).
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	Placebo	Patients received matching placebo for 50 mg, 40 mg or 30 mg afatinib tablets starting with 50 mg/day. Dose reductions were managed in the same way as for the afatinib arm.			36	195	167	195
EG001	Afatinib 50 mg/Day	Patients started with a 50 mg/day dose. Dose reductions were permitted by the protocol to 40 mg/day plus BSC or 30 mg /day plus BSC based upon prespecified Adverse Events and Common Terminology Criteria for Adverse Events (CTCAE) grade (Version 3.0).			136	390	383	390