Table 3:
Grade 1–2 treatment-related treatment-emergent adverse events occurring in ≥10% of patients and all grade 3–5 treatment-related treatment emergent adverse events
| Ramucirumab plus docetaxel (n=258) | Placebo plus docetaxel (n=265) | |||||||
|---|---|---|---|---|---|---|---|---|
| Grade 1–2 | Grade 3 | Grade 4 | Grade 5 | Grade 1–2 | Grade 3 | Grade 4 | Grade 5 | |
| Patients with ≥1 treatment-related treatment-emergent adverse event | 98 (38%) | 86 (33%) | 29 (11%) | 8 (3%) | 115 (43%) | 73 (28%) | 30 (11%) | 5 (2%) |
| Fatigue* | 84 (33%) | 17 (7%) | 0 | 0 | 80 (30%) | 16 (6%) | 0 | 0 |
| Alopecia | 61 (24%) | 0 | 0 | 0 | 80 (30%) | 1 (<1%) | 0 | 0 |
| Diarrhoea | 53 (21%) | 8 (3%) | 0 | 0 | 41 (15%) | 3 (1%) | 0 | 0 |
| Decreased appetite | 53 (21%) | 4 (2%) | 0 | 0 | 44 (17%) | 1 (<1%) | 0 | 0 |
| Nausea | 55 (21%) | 2 (<1%) | 0 | 0 | 35 (13%) | 2 (<1%) | 0 | 0 |
| Stomatitis | 51 (20%) | 9 (3%) | 0 | 0 | 24 (9%) | 0 | 0 | 0 |
| Vomiting | 27 (10%) | 2 (<1%) | 0 | 0 | 25 (9%) | 1 (<1%) | 0 | 0 |
| Hypertension* | 12 (5%) | 11 (4%) | 1 (<1%) | 0 | 6 (2%) | 0 | 0 | 0 |
| Constipation | 16 (6%) | 1 (<1%) | 0 | 0 | 21 (8%) | 0 | 0 | 0 |
| Hyperuricaemia | 3 (1%) | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 |
| Hypokalaemia | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) | 1 (<1%) | 0 | 0 |
| Hypophosphataemia | 1 (<1%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Epistaxis | 31 (12%) | 0 | 0 | 0 | 11 (4%) | 0 | 0 | 0 |
| Pyrexia | 22 (9%) | 1 (<1%) | 0 | 0 | 15 (6%) | 1 (<1%) | 0 | 0 |
| Hyponatraemia | 1 (<1%) | 1 (<1%) | 0 | 0 | 1 (<1%) | 0 | 0 | 0 |
| Dysgeusia | 27 (10%) | 0 | 0 | 0 | 14 (5%) | 0 | 0 | 0 |
| Malaise | 12 (5%) | 1 (<1%) | 0 | 0 | 8 (3%) | 0 | 0 | 0 |
| Mucosal inflammation | 10 (4%) | 3 (1%) | 0 | 0 | 3 (1%) | 1 (<1%) | 0 | 0 |
| Dyspnoea | 7 (3%) | 4 (2%) | 0 | 0 | 10 (4%) | 1 (<1%) | 0 | 0 |
| Pain | 3 (1%) | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Non-cardiac chest pain | 1 (<1%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Neuropathy* | 27 (10%) | 0 | 0 | 0 | 31 (12%) | 3 (1%) | 0 | 0 |
| Abdominal pain* | 10 (4%) | 1 (<1%) | 0 | 0 | 8 (3%) | 0 | 0 | 0 |
| Death (unknown cause) | 0 | 0 | 0 | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) |
| Hepatic failure | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| General physical health deterioration | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Generalised oedema | 1 (<1%) | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Anal fistula | 1 (<1%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Colitis | 1 (<1%) | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Gastric haemorrhage | 0 | 0 | 0 | 1 (<1%) | 0 | 0 | 0 | 0 |
| Small intestinal perforation | 0 | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 |
| Upper gastrointestinal haemorrhage | 1 (<1%) | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Rectal haemorrhage | 1 (<1%) | 0 | 0 | 0 | 2 (<1%) | 1 (<1%) | 0 | 0 |
| Enterovesical fistula | 0 | 0 | 0 | 1 (<1%) | 0 | 0 | 0 | 0 |
| Oesophagitis | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Tooth disorder | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Lymphopenia | 1 (<1%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Neutropenia | 5 (2%) | 8 (3%) | 9 (3%) | 0 | 5 (2%) | 3 (1%) | 3 (1%) | 0 |
| Febrile neutropenia | 0 | 22 (9%) | 2 (<1%) | 0 | 0 | 15 (6%) | 1 (<1%) | 0 |
| Anaemia | 25 (10%) | 5 (2%) | 0 | 0 | 29 (11%) | 14 (5%) | 0 | 0 |
| Leukopenia | 4 (2%) | 2 (<1%) | 1 (<1%) | 0 | 0 | 4 (2%) | 1 (<1%) | 0 |
| Thrombocytopenia | 4 (2%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Haemorrhagic anaemia | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Pancytopenia | 0 | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 |
| Decreased neutrophil count | 7 (3%) | 8 (3%) | 15 (6%) | 0 | 1 (<1%) | 8 (3%) | 19 (7%) | 0 |
| Decreased platelet count | 15 (6%) | 1 (<1%) | 1 (<1%) | 0 | 5 (2%) | 1 (<1%) | 0 | 0 |
| Decreased white blood cell count | 6 (2%) | 6 (2%) | 5 (2%) | 0 | 3 (1%) | 13 (5%) | 4 (2%) | 0 |
| Increased alanine aminotransferase | 4 (2%) | 1 (<1%) | 0 | 0 | 3 (1%) | 1 (<1%) | 0 | 0 |
| Decreased lymphocyte count | 2 (<1%) | 3 (1%) | 0 | 0 | 4 (2%) | 2 (<1%) | 0 | 0 |
| Elevated blood pressure | 0 | 2 (<1%) | 0 | 0 | 1 (<1%) | 0 | 0 | 0 |
| Increased gamma-glutamyltransferase | 0 | 1 (<1%) | 0 | 0 | 0 | 2 (<1%) | 0 | 0 |
| Decreased blood pressure | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Decreased creatinine renal clearance | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Increased lymphocyte count | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Coronary arteriospasm | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Cardiac arrest | 0 | 0 | 0 | 1 (<1%) | 0 | 0 | 0 | 0 |
| Left ventricular dysfunction | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Intracardiac thrombus | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Hypoacusis | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Adrenal insufficiency | 0 | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 |
| Urinary tract infection | 4 (2%) | 3 (1%) | 0 | 0 | 4 (2%) | 2 (<1%) | 0 | 0 |
| Tooth infection | 1 (<1%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Gingivitis | 4 (2%) | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Pneumonia | 0 | 2 (<1%) | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) | 0 |
| Sepsis | 0 | 0 | 2 (<1%) | 1 (<1%) | 1 (<1%) | 1 (<1%) | 4 (2%) | 0 |
| Neutropenic sepsis | 0 | 0 | 0 | 1 (<1%) | 0 | 0 | 0 | 0 |
| Abdominal abscess | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Bronchitis | 1 (<1%) | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Cellulitis | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) | 1 (<1%) | 0 | 0 |
| Clostridium difficile colitis | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Gastroenteritis | 0 | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Pyelonephritis | 0 | 1 (<1%) | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Acute pyelonephritis | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Bacteraemia | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Diverticulitis | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Kidney infection | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Lung infection | 0 | 0 | 0 | 0 | 1 (<1%) | 1 (<1%) | 0 | 1 (<1%) |
| Urosepsis | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 2 (<1%) | 0 |
| Infusion-related reaction | 8 (3%) | 1 (<1%) | 0 | 0 | 7 (3%) | 0 | 0 | 0 |
| Myalgia | 20 (8%) | 1 (<1%) | 0 | 0 | 17 (6%) | 0 | 0 | 0 |
| Arthralgia | 10 (4%) | 0 | 0 | 0 | 9 (3%) | 2 (<1%) | 0 | 0 |
| Back pain | 5 (2%) | 1 (<1%) | 0 | 0 | 2 (<1%) | 0 | 0 | 0 |
| Muscular weakness | 4 (2%) | 0 | 0 | 0 | 3 (1%) | 1 (<1%) | 0 | 0 |
| Lethargy | 2 (<1%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Insomnia | 5 (2%) | 1 (<1%) | 0 | 0 | 4 (2%) | 0 | 0 | 0 |
| Proteinuria | 20 (8%) | 2 (<1%) | 0 | 0 | 8 (3%) | 1 (<1%) | 0 | 0 |
| Haematuria | 12 (5%) | 1 (<1%) | 0 | 0 | 4 (2%) | 1 (<1%) | 0 | 0 |
| Renal failure | 0 | 0 | 0 | 1 (<1%) | 1 (<1%) | 0 | 0 | 0 |
| Female genital tract fistula† | 0 | 1 (2%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Oropharyngeal pain | 6 (2%) | 1 (<1%) | 0 | 0 | 1 (<1%) | 0 | 0 | 0 |
| Pleural effusion | 1 (<1%) | 0 | 0 | 0 | 2 (<1%) | 1 (<1%) | 0 | 0 |
| Pneumonitis | 0 | 1 (<1%) | 0 | 0 | 1 (<1%) | 0 | 0 | 1 (<1%) |
| Laryngeal inflammation | 0 | 0 | 0 | 0 | 0 | 1 (<1%) | 0 | 0 |
| Pulmonary embolism | 0 | 0 | 0 | 0 | 0 | 2 (<1%) | 0 | 1 (<1%) |
| Palmar-plantar erythrodysaesthesia syndrome | 18 (7%) | 1 (<1%) | 0 | 0 | 5 (2%) | 1 (<1%) | 0 | 0 |
| Generalised rash | 1 (<1%) | 1 (<1%) | 0 | 0 | 1 (<1%) | 0 | 0 | 0 |
| Onychalgia | 0 | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Hypotension | 4 (2%) | 0 | 0 | 0 | 2 (<1%) | 1 (<1%) | 0 | 0 |
| Deep vein thrombosis | 2 (<1%) | 1 (<1%) | 0 | 0 | 2 (<1%) | 0 | 0 | 0 |
Data are n (%).
*
Data for drug-related treatment-emergent adverse events are shown as consolidated terms, defined as fatigue (fatigue and asthenia), hypertension (hypertension and increased blood pressure), neuropathy (peripheral sensory neuropathy, peripheral motor neuropathy, peripheral neuropathy, polyneuropathy, hypoaesthesia, and neuralgia), and abdominal pain (abdominal pain and upper abdominal pain).
†
The denominator is adjusted for sex-specific events for women (ramucirumab group n=49; placebo group n=51).