Table 3. Adverse events.
| Cohort 1 (n=26) | Cohort 2 (n=25) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Grade 1–2 | Grade 3 | Grade 4 | Grade 5 | Grade 1–2 | Grade 3 | Grade 4 | Grade 5 | ||
| Rash* | 19 (73%) | 0 | 0 | 0 | 16 (64%) | 1 (4%) | 0 | 0 | |
| Fatigue, asthenia, or malaise† | 18 (69%) | 2 (8%) | 0 | 0 | 16 (64%) | 0 | 0 | 0 | |
| Alopecia | 14 (54%) | 0 | 0 | 0 | 7 (28%) | 0 | 0 | 0 | |
| Dysgeusia | 14 (54%) | 0 | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| Blood creatinine increase | 13 (50%) | 0 | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| Weight decrease | 13 (50%) | 1 (4%) | 0 | 0 | 13 (52%) | 0 | 0 | 0 | |
| Arthralgia | 12 (46%) | 0 | 0 | 0 | 9 (36%) | 0 | 0 | 0 | |
| Decreased appetite | 12 (46%) | 1 (4%) | 0 | 0 | 11 (44%) | 0 | 0 | 0 | |
| Nausea | 12 (46%) | 1 (4%) | 0 | 0 | 7 (28%) | 0 | 0 | 0 | |
| Skin papilloma | 12 (46%) | 1 (4%) | 0 | 0 | 7 (28%) | 0 | 0 | 0 | |
| Diarrhoea | 11 (42%) | 1 (4%) | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| Hyperkeratosis | 11 (42%) | 0 | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| Photosensitivity or sunburn‡ | 11 (42%) | 0 | 0 | 0 | 10 (40%) | 0 | 0 | 0 | |
| Blood bilirubin increase | 10 (38%) | 0 | 0 | 0 | 9 (36%) | 1 (4%) | 0 | 0 | |
| Anaemia | 9 (35%) | 0 | 0 | 0 | 11 (44%) | 2 (8%) | 0 | 0 | |
| Myalgia | 8 (31%) | 1 (4%) | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Blood alkaline phosphatase increase | 7 (27%) | 0 | 0 | 0 | 5 (20%) | 1 (4%) | 0 | 0 | |
| Headache | 7 (27%) | 0 | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Palmar-plantar erythrodysaesthesia | 7 (27%) | 0 | 0 | 0 | 4 (16%) | 2 (8%) | 0 | 0 | |
| Actinic keratosis | 6 (23%) | 1 (4%) | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Dry skin | 6 (23%) | 0 | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| γ-glutamyltransferase increase | 6 (23%) | 1 (4%) | 0 | 0 | 4 (16%) | 2 (8%) | 1 (4%) | 0 | |
| Melanocytic naevus | 6 (23%) | 0 | 0 | 0 | 3 (12%) | 0 | 0 | 0 | |
| Proteinuria | 6 (23%) | 0 | 0 | 0 | 4 (16%) | 0 | 0 | 0 | |
| Skin induration | 6 (23%) | 0 | 0 | 0 | 1 (4%) | 0 | 0 | 0 | |
| Vomiting | 6 (23%) | 0 | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| Acrochordon | 5 (19%) | 0 | 0 | 0 | 1 (4%) | 0 | 0 | 0 | |
| Aspartate aminotransferase increase | 5 (19%) | 0 | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| Cyst | 5 (19%) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Dysphagia | 5 (19%) | 0 | 0 | 0 | 2 (8%) | 1 (4%) | 0 | 0 | |
| Hypertension | 5 (19%) | 1 (4%) | 0 | 0 | 3 (12%) | 0 | 0 | 0 | |
| Hypocalcaemia | 5 (19%) | 0 | 0 | 0 | 4 (16%) | 0 | 0 | 0 | |
| Paraesthesia | 5 (19%) | 0 | 0 | 0 | 1 (4%) | 0 | 0 | 0 | |
| Skin lesion | 5 (19%) | 0 | 0 | 0 | 3 (12%) | 0 | 0 | 0 | |
| Alanine aminotransferase increase | 4 (15%) | 0 | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Conjunctivitis | 4 (15%) | 0 | 0 | 0 | 1 (4%) | 0 | 0 | 0 | |
| Constipation | 4 (15%) | 0 | 0 | 0 | 2 (8%) | 0 | 0 | 0 | |
| Dermal cyst | 4 (15%) | 0 | 0 | 0 | 3 (12%) | 0 | 0 | 0 | |
| Dermatitis acneiform | 4 (15%) | 0 | 0 | 0 | 2 (8%) | 0 | 0 | 0 | |
| Dyspnoea | 3 (12%) | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 1 (4%) | 1 (4%) | |
| Hyperglycaemia | 3 (12%) | 1 (4%) | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Insomnia | 4 (15%) | 0 | 0 | 0 | 3 (12%) | 0 | 0 | 0 | |
| Keratosis pilaris | 4 (15%) | 0 | 0 | 0 | 3 (12%) | 0 | 0 | 0 | |
| Neck pain | 4 (15%) | 0 | 0 | 0 | 1 (4%) | 0 | 0 | 0 | |
| Oedema peripheral | 4 (15%) | 0 | 0 | 0 | 7 (28%) | 0 | 0 | 0 | |
| Pain in extremity | 4 (15%) | 0 | 0 | 0 | 7 (28%) | 0 | 0 | 0 | |
| Back pain | 3 (12%) | 0 | 0 | 0 | 2 (8%) | 1 (4%) | 0 | 0 | |
| Blood uric acid increase | 3 (12%) | 0 | 1 (4%) | 0 | 1 (4%) | 0 | 1 (4%) | 0 | |
| Electrocardiograph QT prolonged | 3 (12%) | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Hyponatraemia | 3 (12%) | 1 (4%) | 0 | 0 | 7 (28%) | 0 | 0 | 0 | |
| Hypokalaemia | 3 (12%) | 0 | 0 | 0 | 5 (20%) | 1 (4%) | 0 | 0 | |
| Lymphopenia | 3 (12%) | 2 (8%) | 0 | 0 | 3 (12%) | 2 (8%) | 0 | 0 | |
| Musculoskeletal pain | 3 (12%) | 0 | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Urinary tract infection | 3 (12%) | 0 | 0 | 0 | 4 (16%) | 0 | 0 | 0 | |
| Dehydration | 2 (8%) | 1 (4%) | 0 | 0 | 4 (16%) | 1 (4%) | 0 | 0 | |
| Dizziness | 2 (8%) | 0 | 0 | 0 | 8 (32%) | 0 | 0 | 0 | |
| Hyperbilirubinaemia | 2 (8%) | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Hypoalbuminaemia | 2 (8%) | 0 | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Pruritus | 2 (8%) | 0 | 0 | 0 | 4 (16%) | 0 | 0 | 0 | |
| White blood cell count decrease | 2 (8%) | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Atrial fibrillation | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Cough | 1 (4%) | 0 | 0 | 0 | 5 (20%) | 0 | 0 | 0 | |
| Hyperuricaemia | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | |
| Hypotension | 1 (4%) | 0 | 0 | 0 | 0 | 1 (4%) | 1 (4%) | 0 | |
| Keratoacanthoma | 1 (4%) | 2 (8%) | 0 | 0 | 2 (8%) | 1 (4%) | 0 | 0 | |
| Pleuritic pain | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Pneumonia | 1 (4%) | 0 | 0 | 0 | 1 (4%) | 2 (8%) | 0 | 0 | |
| Pulmonary haemorrhage | 1 (4%) | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Pyrexia | 1 (4%) | 0 | 0 | 0 | 6 (24%) | 0 | 0 | 0 | |
| Anal haemorrhage | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Angina pectoris | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Basal cell carcinoma | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Blood pressure increase | 0 | 0 | 0 | 0 | 1 (4%) | 1 (4%) | 0 | 0 | |
| Cardiac failure congestive | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Cardiomegaly | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Convulsion | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Diverticulitis | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Food poisoning | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Hepatotoxicity | 0 | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | |
| Large intestine perforation | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Laryngitis | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Lymphocyte count decrease | 0 | 2 (8%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Laryngeal oedema | 0 | 1 (4%) | 0 | 0 | 1 (4%) | 0 | 0 | 0 | |
| Left ventricular dysfunction | 0 | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | |
| Malignant melanoma | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Multiorgan failure | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (4%) | |
| Musculoskeletal chest pain | 0 | 0 | 0 | 0 | 2 (8%) | 1 (4%) | 0 | 0 | |
| Myocardial infarction | 0 | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | |
| Oesophageal haemorrhage | 0 | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | |
| Oral lichen planus | 0 | 1 (4%) | 0 | 0 | 1 (4%) | 0 | 0 | 0 | |
| Performance status decreased | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Pathological fracture | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Radiation necrosis | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Rectal haemorrhage | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Right ventricular failure | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma | 0 | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma of the skin | 0 | 7 (27%) | 0 | 0 | 0 | 4 (16%) | 1 (4%) | 0 | |
| Thermal burn | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Tumour pain | 0 | 0 | 0 | 0 | 1 (4%) | 1 (4%) | 0 | 0 | |
| Viral labyrinthitis | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Radiation necrosis | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Rectal haemorrhage | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Right ventricular failure | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma | 0 | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma of the skin | 0 | 7 (27%) | 0 | 0 | 0 | 4 (16%) | 1 (4%) | 0 | |
| Thermal burn | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Tumour pain | 0 | 0 | 0 | 0 | 1 (4%) | 1 (4%) | 0 | 0 | |
| Viral labyrinthitis | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Radiation necrosis | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Rectal haemorrhage | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Right ventricular failure | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma | 0 | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma of the skin | 0 | 7 (27%) | 0 | 0 | 0 | 4 (16%) | 1 (4%) | 0 | |
| Thermal burn | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Tumour pain | 0 | 0 | 0 | 0 | 1 (4%) | 1 (4%) | 0 | 0 | |
| Viral labyrinthitis | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Radiation necrosis | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Rectal haemorrhage | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Right ventricular failure | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma | 0 | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma of the skin | 0 | 7 (27%) | 0 | 0 | 0 | 4 (16%) | 1 (4%) | 0 | |
| Thermal burn | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Tumour pain | 0 | 0 | 0 | 0 | 1 (4%) | 1 (4%) | 0 | 0 | |
| Viral labyrinthitis | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Radiation necrosis | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Rectal haemorrhage | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
| Right ventricular failure | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma | 0 | 1 (4%) | 1 (4%) | 0 | 0 | 0 | 0 | 0 | |
| Squamous cell carcinoma of the skin | 0 | 7 (27%) | 0 | 0 | 0 | 4 (16%) | 1 (4%) | 0 | |
| Thermal burn | 0 | 1 (4%) | 0 | 0 | 0 | 0 | 0 | 0 | |
| Tumour pain | 0 | 0 | 0 | 0 | 1 (4%) | 1 (4%) | 0 | 0 | |
| Viral labyrinthitis | 0 | 0 | 0 | 0 | 0 | 1 (4%) | 0 | 0 | |
Data are number of adverse events (%). Table shows grade 1–2 adverse events occurring in 15% or more of patients in either cohort and all grade 3–5 adverse events, irrespective of whether it was treatment related. Cohort 1 includes patients who have never received a multikinase inhibitor and cohort 2 included those previously treated with a multikinase inhibitor.
*
Roche/Genentech basket adverse event term: rash (all)—adverse event preferred term of rash papular, drug eruption rash, dermatitis, folliculitis, rash pruritic, rash vesicular, toxic skin eruption, rash erythematosus, rash maculopapular, rash morbilliform, dermatitis bullous, eyelid rash, rash macular, rash follicular, erythema, generalised erythema, rash generalised, rash papulosquamous, rash pustular, dermatitis exfoliative, exfoliative rash, rash maculovesicular, or dermatitis allergic.
†
Roche/Genentech basket adverse event term: adverse event higher level term of asthenic conditions or adverse event preferred term of asthenia, autonomic nervous system imbalance, cachexia, chronic fatigue syndrome, decreased activity, fatigue, lethargy, listless, malaise, or sluggishness.
‡
Roche/Genentech basket adverse event term: adverse event preferred term of photosensitivity reaction or sunburn.