Time Frame |
Up to 70 months from randomization until clinical cutoff of 16 September 2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination).
|
Adverse Event Reporting Description |
Safety Population: All randomized participants who received at least one dose of study treatment and the participants were analyzed based on the treatment they actually received (N=353 in Trastuzumab + Taxane arm, N=361 in Trastuzumab Emtansine, Pertuzumab-placebo arm, N=366 in Trastuzumab emtansine + pertuzumab arm).
|
|
Arm/Group Title
|
Trastuzumab + Taxane
|
Trastuzumab Emtansine + Placebo
|
Trastuzumab Emtansine + Pertuzumab
|
Arm/Group Description |
Participants received trastuzumab p...
|
Participants received trastuzumab e...
|
Participants received trastuzumab e...
|
Arm/Group Description |
Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
|
Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
|
Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
|
|
|
Trastuzumab + Taxane
|
Trastuzumab Emtansine + Placebo
|
Trastuzumab Emtansine + Pertuzumab
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
--/-- |
--/-- |
--/-- |
|
|
Trastuzumab + Taxane
|
Trastuzumab Emtansine + Placebo
|
Trastuzumab Emtansine + Pertuzumab
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
81/353 (22.95%) |
86/361 (23.82%) |
93/366 (25.41%) |
Blood and lymphatic system disorders |
|
|
|
Febrile neutropenia |
13/353 (3.68%) |
0/361 (0.00%) |
0/366 (0.00%) |
Anaemia |
1/353 (0.28%) |
5/361 (1.39%) |
6/366 (1.64%) |
Neutropenia |
5/353 (1.42%) |
0/361 (0.00%) |
0/366 (0.00%) |
Thrombocytopenia |
0/353 (0.00%) |
2/361 (0.55%) |
2/366 (0.55%) |
Hypercoagulation |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Leukopenia |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Cardiac disorders |
|
|
|
Atrial fibrillation |
1/353 (0.28%) |
0/361 (0.00%) |
1/366 (0.27%) |
Cardiac failure |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Cardiac failure congestive |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Myocardial infarction |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Pericardial effusion |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Supraventricular tachycardia |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Ventricular tachycardia |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Acute Myocardial Infarction |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Ear and labyrinth disorders |
|
|
|
Vertigo |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Eye disorders |
|
|
|
Blindness transient |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Macular hole |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Ocular hypertension |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Gastrointestinal disorders |
|
|
|
Diarrhoea |
4/353 (1.13%) |
0/361 (0.00%) |
0/366 (0.00%) |
Vomiting |
1/353 (0.28%) |
0/361 (0.00%) |
4/366 (1.09%) |
Abdominal pain |
2/353 (0.57%) |
1/361 (0.28%) |
0/366 (0.00%) |
Gastritis |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Rectal haemorrhage |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Anal fistula |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Colitis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Diverticulum |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Gastric haemorrhage |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Gastric ulcer |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Gastritis erosive |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Large intestine perforation |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Lower gastrointestinal haemorrhage |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Mallory-Weiss syndrome |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Mouth haemorrhage |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Nausea |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Splenic artery aneurysm |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Umbilical hernia |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Upper gastrointestinal haemorrhage |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Abdominal Discomfort |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Ascites |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Gastrointestinal Haemorrhage |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Haemorrhoidal Haemorrhage |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
General disorders |
|
|
|
Pyrexia |
2/353 (0.57%) |
4/361 (1.11%) |
5/366 (1.37%) |
Fatigue |
3/353 (0.85%) |
1/361 (0.28%) |
1/366 (0.27%) |
Non-cardiac chest pain |
0/353 (0.00%) |
2/361 (0.55%) |
1/366 (0.27%) |
Death |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
General physical health deterioration |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Pain |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Asthenia |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Catheter site haematoma |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Malaise |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Oedema |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Peripheral swelling |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Adverse Drug Reaction |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Sudden Death |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Hepatobiliary disorders |
|
|
|
Cholecystitis |
0/353 (0.00%) |
1/361 (0.28%) |
1/366 (0.27%) |
Hepatic Fibrosis |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Hepatic Haematoma |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Immune system disorders |
|
|
|
Hypersensitivity |
0/353 (0.00%) |
2/361 (0.55%) |
2/366 (0.55%) |
Anaphylactic reaction |
2/353 (0.57%) |
0/361 (0.00%) |
1/366 (0.27%) |
Cytokine release syndrome |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Anaphylactic Shock |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Anaphylactoid Reaction |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Infections and infestations |
|
|
|
Pneumonia |
4/353 (1.13%) |
3/361 (0.83%) |
5/366 (1.37%) |
Cellulitis |
3/353 (0.85%) |
3/361 (0.83%) |
1/366 (0.27%) |
Sepsis |
1/353 (0.28%) |
0/361 (0.00%) |
4/366 (1.09%) |
Device related infection |
0/353 (0.00%) |
1/361 (0.28%) |
1/366 (0.27%) |
Gastroenteritis |
1/353 (0.28%) |
0/361 (0.00%) |
2/366 (0.55%) |
Infection |
1/353 (0.28%) |
1/361 (0.28%) |
1/366 (0.27%) |
Neutropenic sepsis |
3/353 (0.85%) |
0/361 (0.00%) |
0/366 (0.00%) |
Septic shock |
2/353 (0.57%) |
1/361 (0.28%) |
1/366 (0.27%) |
Bronchitis |
0/353 (0.00%) |
0/361 (0.00%) |
3/366 (0.82%) |
Herpes zoster |
2/353 (0.57%) |
0/361 (0.00%) |
0/366 (0.00%) |
Upper respiratory tract infection |
1/353 (0.28%) |
1/361 (0.28%) |
0/366 (0.00%) |
Urinary tract infection |
2/353 (0.57%) |
0/361 (0.00%) |
0/366 (0.00%) |
Wound infection |
1/353 (0.28%) |
1/361 (0.28%) |
0/366 (0.00%) |
Arthritis infective |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Atypical pneumonia |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Breast abscess |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Chorioretinitis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Clostridium difficile colitis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Clostridium difficile infection |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Cystitis |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Empyema |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Erysipelas |
1/353 (0.28%) |
1/361 (0.28%) |
0/366 (0.00%) |
Escherichia sepsis |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Gastroenteritis viral |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Influenza |
1/353 (0.28%) |
1/361 (0.28%) |
0/366 (0.00%) |
Klebsiella sepsis |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Localised infection |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Lower respiratory tract infection |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Lung infection |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Mastitis |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Nasopharyngitis |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Pneumonia pneumococcal |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Rectal abscess |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Respiratory tract infection |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Streptococcal sepsis |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Tooth infection |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Urosepsis |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Abscess Limb |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Appendicitis Perforated |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Catheter Site Infection |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Skin Infection |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Injury, poisoning and procedural complications |
|
|
|
Infusion related reaction |
1/353 (0.28%) |
7/361 (1.94%) |
13/366 (3.55%) |
Femur fracture |
1/353 (0.28%) |
0/361 (0.00%) |
3/366 (0.82%) |
Pubis fracture |
1/353 (0.28%) |
0/361 (0.00%) |
1/366 (0.27%) |
Arterial injury |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Contusion |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Fall |
0/353 (0.00%) |
2/361 (0.55%) |
0/366 (0.00%) |
Femoral neck fracture |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Gastrointestinal stoma complication |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Hip fracture |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Radiation retinopathy |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Spinal compression fracture |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Subdural haematoma |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Wound secretion |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Abdominal Injury |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Foot Fracture |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Fracture |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Stomal Hernia |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Uncoded serious adverse event |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Investigations |
|
|
|
Alanine aminotransferase increased |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Aspartate aminotransferase increased |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Body temperature increased |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
International normalised ratio increased |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Oxygen saturation decreased |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Metabolism and nutrition disorders |
|
|
|
Dehydration |
1/353 (0.28%) |
0/361 (0.00%) |
1/366 (0.27%) |
Hyperglycaemia |
0/353 (0.00%) |
2/361 (0.55%) |
0/366 (0.00%) |
Decreased appetite |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Diabetic ketoacidosis |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Hypercalcaemia |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Hypokalaemia |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Hyponatraemia |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Diabetes Mellitus |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Musculoskeletal and connective tissue disorders |
|
|
|
Arthralgia |
1/353 (0.28%) |
2/361 (0.55%) |
1/366 (0.27%) |
Back pain |
1/353 (0.28%) |
1/361 (0.28%) |
1/366 (0.27%) |
Bone pain |
2/353 (0.57%) |
1/361 (0.28%) |
0/366 (0.00%) |
Intervertebral disc protrusion |
1/353 (0.28%) |
1/361 (0.28%) |
0/366 (0.00%) |
Exostosis |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Musculoskeletal chest pain |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Musculoskeletal pain |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Neck pain |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Pain in extremity |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Pathological fracture |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Rotator cuff syndrome |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Tenosynovitis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
|
|
Acute leukaemia |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Breast neoplasm |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Chronic myeloid leukaemia |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Colon neoplasm |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Lung adenocarcinoma |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Myelodysplastic syndrome |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Squamous cell carcinoma of the cervix |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Tumour haemorrhage |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Uterine leiomyoma |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Basal Cell Carcinoma |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Intracranial Tumour Haemorrhage |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Nervous system disorders |
|
|
|
Headache |
0/353 (0.00%) |
2/361 (0.55%) |
2/366 (0.55%) |
Syncope |
0/353 (0.00%) |
2/361 (0.55%) |
1/366 (0.27%) |
Haemorrhage intracranial |
1/353 (0.28%) |
1/361 (0.28%) |
0/366 (0.00%) |
Cerebrovascular accident |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Cognitive disorder |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Depressed level of consciousness |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Guillain-Barre syndrome |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Lacunar infarction |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Paraparesis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Peripheral sensory neuropathy |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Presyncope |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Somnolence |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Vascular dementia |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Cerebral Haemorrhage |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Epilepsy |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Neuropathy Peripheral |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Sciatica |
1/353 (0.28%) |
0/361 (0.00%) |
1/366 (0.27%) |
Seizure |
1/353 (0.28%) |
1/361 (0.28%) |
1/366 (0.27%) |
Product Issues |
|
|
|
Device Breakage |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Psychiatric disorders |
|
|
|
Confusional state |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Depression |
0/353 (0.00%) |
1/361 (0.28%) |
2/366 (0.55%) |
Anxiety |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Mental Status Changes |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Suicide Attempt |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Renal and urinary disorders |
|
|
|
Calculus urinary |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Reproductive system and breast disorders |
|
|
|
Menorrhagia |
0/353 (0.00%) |
1/361 (0.28%) |
1/366 (0.27%) |
Endometrial hypertrophy |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Vaginal haemorrhage |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Respiratory, thoracic and mediastinal disorders |
|
|
|
Pleural effusion |
3/353 (0.85%) |
1/361 (0.28%) |
3/366 (0.82%) |
Pulmonary embolism |
4/353 (1.13%) |
2/361 (0.55%) |
1/366 (0.27%) |
Dyspnoea |
2/353 (0.57%) |
1/361 (0.28%) |
1/366 (0.27%) |
Epistaxis |
0/353 (0.00%) |
1/361 (0.28%) |
3/366 (0.82%) |
Interstitial lung disease |
1/353 (0.28%) |
1/361 (0.28%) |
1/366 (0.27%) |
Pneumothorax |
0/353 (0.00%) |
0/361 (0.00%) |
2/366 (0.55%) |
Acute respiratory failure |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Alveolitis allergic |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Chronic obstructive pulmonary disease |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Hypoxia |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Nasal turbinate hypertrophy |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Pneumonitis |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Pulmonary fibrosis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Respiratory failure |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Acute Pulmonary Oedema |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Skin and subcutaneous tissue disorders |
|
|
|
Rash |
0/353 (0.00%) |
2/361 (0.55%) |
0/366 (0.00%) |
Dermatomyositis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Peau d'orange |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Cutaneous Lupus Erythematosus |
0/353 (0.00%) |
1/361 (0.28%) |
1/366 (0.27%) |
Vascular disorders |
|
|
|
Hypertension |
1/353 (0.28%) |
1/361 (0.28%) |
0/366 (0.00%) |
Haematoma |
0/353 (0.00%) |
2/361 (0.55%) |
0/366 (0.00%) |
Haemorrhage |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Hypertensive crisis |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Hypotension |
1/353 (0.28%) |
0/361 (0.00%) |
0/366 (0.00%) |
Aneurysm |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Hypovolaemic Shock |
0/353 (0.00%) |
0/361 (0.00%) |
1/366 (0.27%) |
Orthostatic Hypotension |
0/353 (0.00%) |
1/361 (0.28%) |
0/366 (0.00%) |
Indicates events were collected by non-systematic assessment
Term from vocabulary, MedDRA (17.1)
Term from vocabulary, MedDRA (19.0)
Per investigator, this serious adverse event was, "gamma nail implant broke (status after femur fracture)."
|
|
Frequency Threshold for Reporting Other Adverse Events
|
5%
|
|
Trastuzumab + Taxane
|
Trastuzumab Emtansine + Placebo
|
Trastuzumab Emtansine + Pertuzumab
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
342/353 (96.88%) |
352/361 (97.51%) |
352/366 (96.17%) |
Blood and lymphatic system disorders |
|
|
|
Neutropenia |
74/353 (20.96%) |
44/361 (12.19%) |
37/366 (10.11%) |
Anaemia |
39/353 (11.05%) |
48/361 (13.30%) |
59/366 (16.12%) |
Thrombocytopenia |
0/353 (0.00%) |
52/361 (14.40%) |
61/366 (16.67%) |
Ear and labyrinth disorders |
|
|
|
Vertigo |
11/353 (3.12%) |
17/361 (4.71%) |
21/366 (5.74%) |
Eye disorders |
|
|
|
Lacrimation increased |
48/353 (13.60%) |
13/361 (3.60%) |
19/366 (5.19%) |
Dry eye |
13/353 (3.68%) |
25/361 (6.93%) |
24/366 (6.56%) |
Vision Blurred |
10/353 (2.83%) |
13/361 (3.60%) |
19/366 (5.19%) |
Gastrointestinal disorders |
|
|
|
Nausea |
131/353 (37.11%) |
174/361 (48.20%) |
192/366 (52.46%) |
Diarrhoea |
173/353 (49.01%) |
92/361 (25.48%) |
178/366 (48.63%) |
Vomiting |
69/353 (19.55%) |
80/361 (22.16%) |
111/366 (30.33%) |
Constipation |
72/353 (20.40%) |
82/361 (22.71%) |
71/366 (19.40%) |
Stomatitis |
57/353 (16.15%) |
37/361 (10.25%) |
42/366 (11.48%) |
Dyspepsia |
38/353 (10.76%) |
33/361 (9.14%) |
48/366 (13.11%) |
Abdominal pain upper |
31/353 (8.78%) |
39/361 (10.80%) |
46/366 (12.57%) |
Dry mouth |
13/353 (3.68%) |
52/361 (14.40%) |
45/366 (12.30%) |
Abdominal pain |
31/353 (8.78%) |
35/361 (9.70%) |
41/366 (11.20%) |
Gingival bleeding |
4/353 (1.13%) |
31/361 (8.59%) |
25/366 (6.83%) |
Haemorrhoids |
9/353 (2.55%) |
12/361 (3.32%) |
22/366 (6.01%) |
General disorders |
|
|
|
Fatigue |
128/353 (36.26%) |
120/361 (33.24%) |
130/366 (35.52%) |
Pyrexia |
59/353 (16.71%) |
96/361 (26.59%) |
118/366 (32.24%) |
Asthenia |
57/353 (16.15%) |
62/361 (17.17%) |
63/366 (17.21%) |
Chills |
14/353 (3.97%) |
55/361 (15.24%) |
97/366 (26.50%) |
Oedema peripheral |
98/353 (27.76%) |
37/361 (10.25%) |
35/366 (9.56%) |
Mucosal inflammation |
40/353 (11.33%) |
29/361 (8.03%) |
36/366 (9.84%) |
Influenza like illness |
17/353 (4.82%) |
31/361 (8.59%) |
32/366 (8.74%) |
Non-cardiac chest pain |
24/353 (6.80%) |
25/361 (6.93%) |
27/366 (7.38%) |
Pain |
29/353 (8.22%) |
26/361 (7.20%) |
19/366 (5.19%) |
Oedema |
31/353 (8.78%) |
11/361 (3.05%) |
3/366 (0.82%) |
Infections and infestations |
|
|
|
Upper respiratory tract infection |
55/353 (15.58%) |
50/361 (13.85%) |
66/366 (18.03%) |
Nasopharyngitis |
49/353 (13.88%) |
52/361 (14.40%) |
66/366 (18.03%) |
Urinary tract infection |
29/353 (8.22%) |
31/361 (8.59%) |
41/366 (11.20%) |
Rhinitis |
18/353 (5.10%) |
25/361 (6.93%) |
24/366 (6.56%) |
Influenza |
14/353 (3.97%) |
22/361 (6.09%) |
25/366 (6.83%) |
Paronychia |
22/353 (6.23%) |
8/361 (2.22%) |
30/366 (8.20%) |
Pharyngitis |
14/353 (3.97%) |
19/361 (5.26%) |
17/366 (4.64%) |
Conjunctivitis |
21/353 (5.95%) |
14/361 (3.88%) |
17/366 (4.64%) |
Bronchitis |
14/353 (3.97%) |
9/361 (2.49%) |
20/366 (5.46%) |
Investigations |
|
|
|
Aspartate aminotransferase increased |
9/353 (2.55%) |
54/361 (14.96%) |
28/366 (7.65%) |
Alanine aminotranseferase increased |
10/353 (2.83%) |
41/361 (11.36%) |
35/366 (9.56%) |
Weight decreased |
7/353 (1.98%) |
24/361 (6.65%) |
30/366 (8.20%) |
Ejection fraction decreased |
31/353 (8.78%) |
7/361 (1.94%) |
16/366 (4.37%) |
Gamma- glutamyltranseferase increased |
1/353 (0.28%) |
30/361 (8.31%) |
17/366 (4.64%) |
Metabolism and nutrition disorders |
|
|
|
Decreased appetite |
76/353 (21.53%) |
84/361 (23.27%) |
84/366 (22.95%) |
Hypokalaemia |
15/353 (4.25%) |
19/361 (5.26%) |
30/366 (8.20%) |
Musculoskeletal and connective tissue disorders |
|
|
|
Arthralgia |
91/353 (25.78%) |
83/361 (22.99%) |
71/366 (19.40%) |
Myalgia |
82/353 (23.23%) |
66/361 (18.28%) |
61/366 (16.67%) |
Back pain |
46/353 (13.03%) |
60/361 (16.62%) |
63/366 (17.21%) |
Pain in extremity |
48/353 (13.60%) |
53/361 (14.68%) |
54/366 (14.75%) |
Muscle spasms |
15/353 (4.25%) |
32/361 (8.86%) |
62/366 (16.94%) |
Musculoskeletal pain |
23/353 (6.52%) |
30/361 (8.31%) |
37/366 (10.11%) |
Bone pain |
33/353 (9.35%) |
17/361 (4.71%) |
29/366 (7.92%) |
Musculoskeletal chest pain |
17/353 (4.82%) |
13/361 (3.60%) |
20/366 (5.46%) |
Neck Pain |
12/353 (3.40%) |
12/361 (3.32%) |
24/366 (6.56%) |
Nervous system disorders |
|
|
|
Headache |
80/353 (22.66%) |
116/361 (32.13%) |
120/366 (32.79%) |
Neuropathy peripheral |
99/353 (28.05%) |
52/361 (14.40%) |
69/366 (18.85%) |
Peripheral sensory neuropathy |
70/353 (19.83%) |
47/361 (13.02%) |
46/366 (12.57%) |
Dysgeusia |
54/353 (15.30%) |
30/361 (8.31%) |
50/366 (13.66%) |
Paraesthesia |
41/353 (11.61%) |
31/361 (8.59%) |
43/366 (11.75%) |
Dizziness |
35/353 (9.92%) |
38/361 (10.53%) |
38/366 (10.38%) |
Psychiatric disorders |
|
|
|
Insomnia |
51/353 (14.45%) |
51/361 (14.13%) |
52/366 (14.21%) |
Anxiety |
22/353 (6.23%) |
26/361 (7.20%) |
33/366 (9.02%) |
Depression |
17/353 (4.82%) |
34/361 (9.42%) |
20/366 (5.46%) |
Reproductive system and breast disorders |
|
|
|
Breast pain |
18/353 (5.10%) |
13/361 (3.60%) |
16/366 (4.37%) |
Respiratory, thoracic and mediastinal disorders |
|
|
|
Epistaxis |
53/353 (15.01%) |
113/361 (31.30%) |
127/366 (34.70%) |
Cough |
74/353 (20.96%) |
72/361 (19.94%) |
79/366 (21.58%) |
Dyspnoea |
56/353 (15.86%) |
42/361 (11.63%) |
53/366 (14.48%) |
Oropharyngeal pain |
29/353 (8.22%) |
31/361 (8.59%) |
30/366 (8.20%) |
Rhinorrhoea |
26/353 (7.37%) |
21/361 (5.82%) |
32/366 (8.74%) |
Skin and subcutaneous tissue disorders |
|
|
|
Alopecia |
212/353 (60.06%) |
26/361 (7.20%) |
33/366 (9.02%) |
Rash |
86/353 (24.36%) |
62/361 (17.17%) |
89/366 (24.32%) |
Pruritus |
32/353 (9.07%) |
28/361 (7.76%) |
51/366 (13.93%) |
Nail disorder |
39/353 (11.05%) |
11/361 (3.05%) |
19/366 (5.19%) |
Dry skin |
24/353 (6.80%) |
24/361 (6.65%) |
29/366 (7.92%) |
Erythema |
24/353 (6.80%) |
13/361 (3.60%) |
20/366 (5.46%) |
Dermatitis acneiform |
6/353 (1.70%) |
16/361 (4.43%) |
27/366 (7.38%) |
Palmar-plantar erythrodysaesthesia syndrome |
26/353 (7.37%) |
6/361 (1.66%) |
11/366 (3.01%) |
Nail discolouration |
25/353 (7.08%) |
5/361 (1.39%) |
1/366 (0.27%) |
Onychoclasis |
13/353 (3.68%) |
19/361 (5.26%) |
17/366 (4.64%) |
Vascular disorders |
|
|
|
Hypertension |
19/353 (5.38%) |
37/361 (10.25%) |
43/366 (11.75%) |
Hot flush |
27/353 (7.65%) |
16/361 (4.43%) |
12/366 (3.28%) |
Lymphoedema |
27/353 (7.65%) |
7/361 (1.94%) |
8/366 (2.19%) |
Indicates events were collected by systematic assessment
Indicates events were collected by non-systematic assessment
Term from vocabulary, MedDRA (17.1)
Term from vocabulary, MedDRA (19.0)
|