Time Frame |
From first administration of treatment until 28 days after last drug administration, upto 51 Months (Part A) and from randomization until 28 days after last drug administration of Trial medication, upto 32 Months (Part B).
|
Adverse Event Reporting Description |
Part A-events that started within the period defined by the first administration of afatinib until randomization into Part B or 28 days after the last administration of afatinib, whichever occurred first. Part B-events that started within the period from randomization through 28 days after the last administration of trial medication.
|
|
Arm/Group Title
|
Afatinib Monotherapy (Part A)
|
Afatinib Plus Paclitaxel (Part B)
|
Investigators Choice of Chemotherapy (Part B)
|
Arm/Group Description |
Afatinib 50 mg film-coated tablet w...
|
Afatinib 40 mg film-coated tablet d...
|
Reference therapy for Part B dose: ...
|
Arm/Group Description |
Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).
|
Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
|
Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
|
|
|
Afatinib Monotherapy (Part A)
|
Afatinib Plus Paclitaxel (Part B)
|
Investigators Choice of Chemotherapy (Part B)
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
--/-- |
--/-- |
--/-- |
|
|
Afatinib Monotherapy (Part A)
|
Afatinib Plus Paclitaxel (Part B)
|
Investigators Choice of Chemotherapy (Part B)
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
471/1154 (40.81%) |
54/134 (40.30%) |
19/60 (31.67%) |
Blood and lymphatic system disorders |
|
|
|
Anaemia |
4/1154 (0.35%) |
1/134 (0.75%) |
0/60 (0.00%) |
Febrile neutropenia |
0/1154 (0.00%) |
1/134 (0.75%) |
1/60 (1.67%) |
Leukopenia |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Neutropenia |
0/1154 (0.00%) |
1/134 (0.75%) |
1/60 (1.67%) |
Disseminated intravascular coagulation |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Thrombocytopenia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cardiac disorders |
|
|
|
Arrhythmia |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Acute coronary syndrome |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Acute left ventricular failure |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Atrial fibrillation |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Atrioventricular block complete |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Bradycardia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cardiac failure |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cardiac tamponade |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cardiopulmonary failure |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Coronary artery disease |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Left ventricular dysfunction |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Myocardial infarction |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pericardial effusion |
5/1154 (0.43%) |
0/134 (0.00%) |
0/60 (0.00%) |
Tachycardia |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Congenital, familial and genetic disorders |
|
|
|
Tracheo-oesophageal fistula |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Ear and labyrinth disorders |
|
|
|
Vertigo |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Eye disorders |
|
|
|
Diplopia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Retinal detachment |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Vision blurred |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Gastrointestinal disorders |
|
|
|
Abdominal pain |
6/1154 (0.52%) |
2/134 (1.49%) |
1/60 (1.67%) |
Ascites |
4/1154 (0.35%) |
1/134 (0.75%) |
0/60 (0.00%) |
Diarrhoea |
59/1154 (5.11%) |
6/134 (4.48%) |
0/60 (0.00%) |
Gastrointestinal disorder |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Gingival bleeding |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Haemorrhoids |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Nausea |
8/1154 (0.69%) |
1/134 (0.75%) |
0/60 (0.00%) |
Pancreatitis |
2/1154 (0.17%) |
1/134 (0.75%) |
0/60 (0.00%) |
Rectal haemorrhage |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Rectal prolapse |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Vomiting |
18/1154 (1.56%) |
1/134 (0.75%) |
0/60 (0.00%) |
Abdominal pain upper |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Constipation |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Duodenal ulcer |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Dysphagia |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Epigastric discomfort |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Gastritis haemorrhagic |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Gastrointestinal hypomotility |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Gastrooesophageal reflux disease |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Haematemesis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Ileus |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Ileus paralytic |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Intestinal obstruction |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Jejunal perforation |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pancreatitis acute |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Peritoneal haemorrhage |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Small intestinal obstruction |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Stomatitis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Vomiting projectile |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
General disorders |
|
|
|
Adverse drug reaction |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Asthenia |
8/1154 (0.69%) |
1/134 (0.75%) |
0/60 (0.00%) |
Chest pain |
8/1154 (0.69%) |
1/134 (0.75%) |
1/60 (1.67%) |
Extravasation |
0/1154 (0.00%) |
0/134 (0.00%) |
1/60 (1.67%) |
General physical health deterioration |
45/1154 (3.90%) |
7/134 (5.22%) |
1/60 (1.67%) |
Pyrexia |
9/1154 (0.78%) |
1/134 (0.75%) |
1/60 (1.67%) |
Chest discomfort |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Death |
5/1154 (0.43%) |
0/134 (0.00%) |
0/60 (0.00%) |
Fatigue |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Gravitational oedema |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hyperthermia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Local swelling |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Malaise |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Mucosal inflammation |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Multi-organ failure |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Oedema |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pain |
5/1154 (0.43%) |
0/134 (0.00%) |
0/60 (0.00%) |
Performance status decreased |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Sudden death |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hepatobiliary disorders |
|
|
|
Bile duct obstruction |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cholangitis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cholestasis |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hepatic failure |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hepatic mass |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hepatic pain |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hepatitis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Liver injury |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Infections and infestations |
|
|
|
Bacterial infection |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Bronchitis |
2/1154 (0.17%) |
2/134 (1.49%) |
0/60 (0.00%) |
Cellulitis |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Empyema |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Infectious pleural effusion |
1/1154 (0.09%) |
1/134 (0.75%) |
0/60 (0.00%) |
Lower respiratory tract infection |
5/1154 (0.43%) |
2/134 (1.49%) |
0/60 (0.00%) |
Nasopharyngitis |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Pneumonia |
42/1154 (3.64%) |
4/134 (2.99%) |
3/60 (5.00%) |
Pneumonia bacterial |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Respiratory tract infection |
5/1154 (0.43%) |
3/134 (2.24%) |
0/60 (0.00%) |
Urinary tract infection |
2/1154 (0.17%) |
1/134 (0.75%) |
0/60 (0.00%) |
Aspergillus infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Catheter site infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Device related infection |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Endocarditis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Erysipelas |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Escherichia sepsis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Fungal infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Gastroenteritis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Herpes zoster |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Infection |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Kidney infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Laryngitis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Lobar pneumonia |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Localised infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Lung abscess |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Lung infection |
11/1154 (0.95%) |
0/134 (0.00%) |
0/60 (0.00%) |
Lymphangitis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Meningitis bacterial |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Paronychia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Peritonitis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Respiratory tract infection viral |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Sepsis |
5/1154 (0.43%) |
0/134 (0.00%) |
0/60 (0.00%) |
Septic shock |
5/1154 (0.43%) |
0/134 (0.00%) |
0/60 (0.00%) |
Skin bacterial infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Staphylococcal infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Staphylococcal skin infection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Upper respiratory tract infection |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Urosepsis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Injury, poisoning and procedural complications |
|
|
|
Fracture displacement |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Overdose |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Compression fracture |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Fall |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Femoral neck fracture |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Femur fracture |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Ligament sprain |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pelvic fracture |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Post procedural complication |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Road traffic accident |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Spinal compression fracture |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Investigations |
|
|
|
Biopsy lymph gland abnormal |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Gene mutation identification test |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Weight decreased |
0/1154 (0.00%) |
2/134 (1.49%) |
0/60 (0.00%) |
Glomerular filtration rate decreased |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Haemoglobin decreased |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Oxygen saturation decreased |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Staphylococcus test positive |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Metabolism and nutrition disorders |
|
|
|
Decreased appetite |
12/1154 (1.04%) |
2/134 (1.49%) |
0/60 (0.00%) |
Dehydration |
15/1154 (1.30%) |
1/134 (0.75%) |
0/60 (0.00%) |
Fluid retention |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hypokalaemia |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hyponatraemia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hypophosphataemia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hypoproteinaemia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hypovolaemia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Musculoskeletal and connective tissue disorders |
|
|
|
Back pain |
11/1154 (0.95%) |
1/134 (0.75%) |
0/60 (0.00%) |
Musculoskeletal chest pain |
2/1154 (0.17%) |
1/134 (0.75%) |
0/60 (0.00%) |
Osteoporosis |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Spinal pain |
2/1154 (0.17%) |
1/134 (0.75%) |
0/60 (0.00%) |
Arthralgia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Bone pain |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Intervertebral disc protrusion |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Mobility decreased |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Muscular weakness |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Musculoskeletal pain |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Neck pain |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Osteonecrosis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pain in extremity |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pathological fracture |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
|
|
Malignant neoplasm progression |
46/1154 (3.99%) |
2/134 (1.49%) |
0/60 (0.00%) |
Metastases to central nervous system |
7/1154 (0.61%) |
3/134 (2.24%) |
1/60 (1.67%) |
Metastases to meninges |
2/1154 (0.17%) |
2/134 (1.49%) |
0/60 (0.00%) |
Metastasis |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Neoplasm progression |
19/1154 (1.65%) |
2/134 (1.49%) |
2/60 (3.33%) |
Pericarditis malignant |
1/1154 (0.09%) |
1/134 (0.75%) |
0/60 (0.00%) |
Brain neoplasm |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Lung neoplasm |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Malignant ascites |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Malignant neoplasm of pleura |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Malignant pleural effusion |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Metastases to bone |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Metastases to liver |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Metastases to peritoneum |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Metastases to pleura |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Metastases to spine |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Metastatic pain |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Non-small cell lung cancer |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Parathyroid tumour benign |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Tumour compression |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Tumour pain |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Nervous system disorders |
|
|
|
Cognitive disorder |
1/1154 (0.09%) |
1/134 (0.75%) |
0/60 (0.00%) |
Headache |
2/1154 (0.17%) |
1/134 (0.75%) |
0/60 (0.00%) |
Hydrocephalus |
0/1154 (0.00%) |
0/134 (0.00%) |
1/60 (1.67%) |
Intracranial pressure increased |
3/1154 (0.26%) |
1/134 (0.75%) |
0/60 (0.00%) |
Nervous system disorder |
1/1154 (0.09%) |
0/134 (0.00%) |
1/60 (1.67%) |
Seizure |
6/1154 (0.52%) |
1/134 (0.75%) |
1/60 (1.67%) |
Altered state of consciousness |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Ataxia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Brain oedema |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cerebral haemorrhage |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cerebrovascular accident |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cervicobrachial syndrome |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Dizziness |
5/1154 (0.43%) |
0/134 (0.00%) |
0/60 (0.00%) |
Dysarthria |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Epilepsy |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Monoplegia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Paraparesis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Reversible ischaemic neurological deficit |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Sciatica |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Somnolence |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Speech disorder |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Spinal cord compression |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Syncope |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Psychiatric disorders |
|
|
|
Completed suicide |
1/1154 (0.09%) |
0/134 (0.00%) |
1/60 (1.67%) |
Confusional state |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Depression |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Mental status changes |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Renal and urinary disorders |
|
|
|
Acute kidney injury |
9/1154 (0.78%) |
1/134 (0.75%) |
0/60 (0.00%) |
Renal failure |
4/1154 (0.35%) |
1/134 (0.75%) |
0/60 (0.00%) |
Anuria |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Haematuria |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Renal colic |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Urinary retention |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Respiratory, thoracic and mediastinal disorders |
|
|
|
Dyspnoea |
67/1154 (5.81%) |
5/134 (3.73%) |
3/60 (5.00%) |
Haemoptysis |
7/1154 (0.61%) |
1/134 (0.75%) |
0/60 (0.00%) |
Hypercapnia |
0/1154 (0.00%) |
0/134 (0.00%) |
1/60 (1.67%) |
Interstitial lung disease |
6/1154 (0.52%) |
1/134 (0.75%) |
1/60 (1.67%) |
Lung disorder |
1/1154 (0.09%) |
2/134 (1.49%) |
0/60 (0.00%) |
Pleural effusion |
49/1154 (4.25%) |
3/134 (2.24%) |
1/60 (1.67%) |
Pneumothorax |
6/1154 (0.52%) |
2/134 (1.49%) |
0/60 (0.00%) |
Pulmonary embolism |
17/1154 (1.47%) |
4/134 (2.99%) |
1/60 (1.67%) |
Respiratory arrest |
1/1154 (0.09%) |
1/134 (0.75%) |
0/60 (0.00%) |
Respiratory failure |
13/1154 (1.13%) |
1/134 (0.75%) |
0/60 (0.00%) |
Acute pulmonary oedema |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Acute respiratory distress syndrome |
8/1154 (0.69%) |
0/134 (0.00%) |
0/60 (0.00%) |
Acute respiratory failure |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Asphyxia |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Atelectasis |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Choking |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Chronic obstructive pulmonary disease |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Cough |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Haemothorax |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hydrothorax |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hypoxia |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Obstructive airways disorder |
3/1154 (0.26%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pleural fibrosis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pneumonia aspiration |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pneumonitis |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Productive cough |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pulmonary haemorrhage |
4/1154 (0.35%) |
0/134 (0.00%) |
0/60 (0.00%) |
Pulmonary oedema |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Respiratory acidosis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Thoracic haemorrhage |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Skin and subcutaneous tissue disorders |
|
|
|
Petechiae |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Rash |
1/1154 (0.09%) |
1/134 (0.75%) |
0/60 (0.00%) |
Rash erythematous |
0/1154 (0.00%) |
1/134 (0.75%) |
0/60 (0.00%) |
Skin erosion |
0/1154 (0.00%) |
0/134 (0.00%) |
1/60 (1.67%) |
Decubitus ulcer |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Dermatitis acneiform |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Skin toxicity |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Surgical and medical procedures |
|
|
|
Lung transplant |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Partial lung resection |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Vascular disorders |
|
|
|
Shock |
2/1154 (0.17%) |
1/134 (0.75%) |
0/60 (0.00%) |
Deep vein thrombosis |
6/1154 (0.52%) |
0/134 (0.00%) |
0/60 (0.00%) |
Embolism |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Haemorrhage |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Hypotension |
2/1154 (0.17%) |
0/134 (0.00%) |
0/60 (0.00%) |
Neurogenic shock |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Phlebitis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Raynaud's phenomenon |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Superior vena cava syndrome |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Thrombosis |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Venous thrombosis limb |
1/1154 (0.09%) |
0/134 (0.00%) |
0/60 (0.00%) |
Indicates events were collected by systematic assessment
Term from vocabulary, MedDRA 18.1
|
|
Frequency Threshold for Reporting Other Adverse Events
|
5%
|
|
Afatinib Monotherapy (Part A)
|
Afatinib Plus Paclitaxel (Part B)
|
Investigators Choice of Chemotherapy (Part B)
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
1129/1154 (97.83%) |
128/134 (95.52%) |
50/60 (83.33%) |
Blood and lymphatic system disorders |
|
|
|
Anaemia |
80/1154 (6.93%) |
33/134 (24.63%) |
6/60 (10.00%) |
Leukopenia |
5/1154 (0.43%) |
20/134 (14.93%) |
7/60 (11.67%) |
Neutropenia |
7/1154 (0.61%) |
26/134 (19.40%) |
8/60 (13.33%) |
Gastrointestinal disorders |
|
|
|
Abdominal pain |
90/1154 (7.80%) |
11/134 (8.21%) |
4/60 (6.67%) |
Abdominal pain upper |
65/1154 (5.63%) |
19/134 (14.18%) |
4/60 (6.67%) |
Constipation |
85/1154 (7.37%) |
22/134 (16.42%) |
10/60 (16.67%) |
Diarrhoea |
964/1154 (83.54%) |
72/134 (53.73%) |
4/60 (6.67%) |
Nausea |
252/1154 (21.84%) |
28/134 (20.90%) |
14/60 (23.33%) |
Stomatitis |
303/1154 (26.26%) |
14/134 (10.45%) |
2/60 (3.33%) |
Vomiting |
211/1154 (18.28%) |
31/134 (23.13%) |
4/60 (6.67%) |
Mouth ulceration |
91/1154 (7.89%) |
2/134 (1.49%) |
0/60 (0.00%) |
General disorders |
|
|
|
Asthenia |
200/1154 (17.33%) |
47/134 (35.07%) |
18/60 (30.00%) |
Chest pain |
82/1154 (7.11%) |
9/134 (6.72%) |
2/60 (3.33%) |
Fatigue |
136/1154 (11.79%) |
32/134 (23.88%) |
10/60 (16.67%) |
Mucosal inflammation |
200/1154 (17.33%) |
13/134 (9.70%) |
0/60 (0.00%) |
Oedema peripheral |
57/1154 (4.94%) |
12/134 (8.96%) |
2/60 (3.33%) |
Pyrexia |
82/1154 (7.11%) |
18/134 (13.43%) |
7/60 (11.67%) |
Infections and infestations |
|
|
|
Bronchitis |
21/1154 (1.82%) |
7/134 (5.22%) |
2/60 (3.33%) |
Conjunctivitis |
79/1154 (6.85%) |
12/134 (8.96%) |
0/60 (0.00%) |
Nasopharyngitis |
35/1154 (3.03%) |
10/134 (7.46%) |
2/60 (3.33%) |
Paronychia |
342/1154 (29.64%) |
23/134 (17.16%) |
0/60 (0.00%) |
Pneumonia |
68/1154 (5.89%) |
8/134 (5.97%) |
1/60 (1.67%) |
Rhinitis |
54/1154 (4.68%) |
7/134 (5.22%) |
4/60 (6.67%) |
Upper respiratory tract infection |
32/1154 (2.77%) |
7/134 (5.22%) |
1/60 (1.67%) |
Urinary tract infection |
62/1154 (5.37%) |
14/134 (10.45%) |
1/60 (1.67%) |
Folliculitis |
86/1154 (7.45%) |
5/134 (3.73%) |
0/60 (0.00%) |
Investigations |
|
|
|
Alanine aminotransferase increased |
28/1154 (2.43%) |
8/134 (5.97%) |
2/60 (3.33%) |
Haemoglobin decreased |
11/1154 (0.95%) |
7/134 (5.22%) |
0/60 (0.00%) |
Weight decreased |
132/1154 (11.44%) |
16/134 (11.94%) |
3/60 (5.00%) |
Metabolism and nutrition disorders |
|
|
|
Decreased appetite |
304/1154 (26.34%) |
37/134 (27.61%) |
10/60 (16.67%) |
Hypokalaemia |
51/1154 (4.42%) |
12/134 (8.96%) |
3/60 (5.00%) |
Musculoskeletal and connective tissue disorders |
|
|
|
Arthralgia |
46/1154 (3.99%) |
8/134 (5.97%) |
2/60 (3.33%) |
Back pain |
94/1154 (8.15%) |
8/134 (5.97%) |
5/60 (8.33%) |
Musculoskeletal pain |
48/1154 (4.16%) |
8/134 (5.97%) |
0/60 (0.00%) |
Myalgia |
17/1154 (1.47%) |
10/134 (7.46%) |
7/60 (11.67%) |
Pain in extremity |
60/1154 (5.20%) |
8/134 (5.97%) |
5/60 (8.33%) |
Nervous system disorders |
|
|
|
Dizziness |
60/1154 (5.20%) |
13/134 (9.70%) |
4/60 (6.67%) |
Dysgeusia |
25/1154 (2.17%) |
7/134 (5.22%) |
4/60 (6.67%) |
Headache |
56/1154 (4.85%) |
16/134 (11.94%) |
6/60 (10.00%) |
Hypoaesthesia |
6/1154 (0.52%) |
9/134 (6.72%) |
5/60 (8.33%) |
Neuropathy peripheral |
8/1154 (0.69%) |
16/134 (11.94%) |
7/60 (11.67%) |
Paraesthesia |
25/1154 (2.17%) |
13/134 (9.70%) |
2/60 (3.33%) |
Peripheral sensory neuropathy |
4/1154 (0.35%) |
8/134 (5.97%) |
2/60 (3.33%) |
Psychiatric disorders |
|
|
|
Insomnia |
39/1154 (3.38%) |
9/134 (6.72%) |
1/60 (1.67%) |
Respiratory, thoracic and mediastinal disorders |
|
|
|
Cough |
194/1154 (16.81%) |
32/134 (23.88%) |
13/60 (21.67%) |
Dysphonia |
36/1154 (3.12%) |
7/134 (5.22%) |
2/60 (3.33%) |
Dyspnoea |
194/1154 (16.81%) |
34/134 (25.37%) |
11/60 (18.33%) |
Epistaxis |
151/1154 (13.08%) |
19/134 (14.18%) |
3/60 (5.00%) |
Oropharyngeal pain |
30/1154 (2.60%) |
10/134 (7.46%) |
1/60 (1.67%) |
Productive cough |
47/1154 (4.07%) |
6/134 (4.48%) |
4/60 (6.67%) |
Rhinorrhoea |
61/1154 (5.29%) |
6/134 (4.48%) |
4/60 (6.67%) |
Skin and subcutaneous tissue disorders |
|
|
|
Alopecia |
39/1154 (3.38%) |
47/134 (35.07%) |
10/60 (16.67%) |
Nail disorder |
41/1154 (3.55%) |
9/134 (6.72%) |
2/60 (3.33%) |
Pruritus |
179/1154 (15.51%) |
13/134 (9.70%) |
3/60 (5.00%) |
Rash |
629/1154 (54.51%) |
30/134 (22.39%) |
7/60 (11.67%) |
Skin fissures |
101/1154 (8.75%) |
10/134 (7.46%) |
1/60 (1.67%) |
Acne |
87/1154 (7.54%) |
5/134 (3.73%) |
0/60 (0.00%) |
Dry skin |
164/1154 (14.21%) |
6/134 (4.48%) |
0/60 (0.00%) |
Palmar-plantar erythrodysaesthesia syndrome |
71/1154 (6.15%) |
2/134 (1.49%) |
0/60 (0.00%) |
Indicates events were collected by systematic assessment
Term from vocabulary, MedDRA 18.1
|