Table 3:
Treatment-related adverse events
| NTRK fusion-positive safety-evaluable population* (n=68) | Overall safety-evaluable population† (n=355) | |||||
|---|---|---|---|---|---|---|
| Grade 1–2 | Grade 3 | Grade 4 | Grade 1–2 | Grade 3 | Grade 4 | |
| Dysgeusia | 32 (47%) | 0 | 0 | 146 (41%) | 1 (<1%) | 0 |
| Constipation | 19 (28%) | 0 | 0 | 83 (23%) | 1 (<1%) | 0 |
| Fatigue | 19 (28%) | 5 (7%) | 0 | 89 (25%) | 10 (3%) | 0 |
| Diarrhoea | 18 (27%) | 1 (2%) | 0 | 76 (21%) | 5 (1%) | 0 |
| Oedema peripheral | 16 (24%) | 1 (2%) | 0 | 49 (14%) | 1 (<1%) | 0 |
| Dizziness | 16 (24%) | 1 (2%) | 0 | 88 (25%) | 2 (1%) | 0 |
| Blood creatinine increased | 12 (18%) | 1 (2%) | 0 | 52 (15%) | 2 (1%) | 0 |
| Paraesthesia | 11 (16%) | 0 | 0 | 67 (19%) | 0 | 0 |
| Nausea | 10 (15%) | 0 | 0 | 74 (21%) | 0 | 0 |
| Vomiting | 9 (13%) | 0 | 0 | 48 (14%) | 0 | 0 |
| Arthralgia | 8 (12%) | 0 | 0 | 42 (12%) | 2 (1%) | 0 |
| Myalgia | 8 (12%) | 0 | 0 | 52 (15%) | 2 (1%) | 0 |
| Weight increased | 8 (12%) | 7 (10%) | 0 | 51 (14%) | 18 (5%) | 0 |
| AST increased | 7 (10%) | 0 | 1 (2%) | 35 (10%) | 3 (1%) | 1 (<1%) |
| ALT increased | 6 (9%) | 0 | 1 (2%) | 30 (9%) | 3 (1%) | 1 (<1%) |
| Muscular weakness | 6 (9%) | 1 (2%) | 0 | 22 (6%) | 3 (1%) | 0 |
| Anaemia | 5 (7%) | 8 (12%) | 0 | 27 (10%) | 16 (5%) | 0 |
| Asthenia | 5 (7%) | 0 | 0 | 28 (8%) | 2 (1%) | 0 |
| Peripheral sensory neuropathy | 4 (6%) | 1 (2%) | 0 | 20 (6%) | 4 (1%) | 0 |
| Neutrophil count decreased | 4 (6%) | 0 | 0 | 13 (4%) | 8 (2%) | 0 |
| Rash | 4 (6%) | 0 | 0 | 18 (5%) | 2 (1%) | 0 |
| Disturbance in attention | 3 (4%) | 0 | 0 | 13 (4%) | 1 (<1%) | 0 |
| Pain of skin | 3 (4%) | 0 | 0 | 9 (3%) | 1 (<1%) | 0 |
| Neutropenia | 3 (4%) | 2 (3%) | 0 | 9 (3%) | 9 (3%) | 0 |
| Localised oedema | 2 (3%) | 1 (2%) | 0 | 3 (1%) | 1 (<1%) | 0 |
| Hyperaesthesia | 2 (3%) | 0 | 0 | 22 (6%) | 1 (<1%) | 0 |
| Ataxia | 2 (3%) | 0 | 0 | 9 (3%) | 3 (1%) | 0 |
| Platelet count decreased | 2 (3%) | 0 | 0 | 4 (1%) | 0 | 1 (<1%) |
| Hyperuricaemia | 2 (3%) | 0 | 2 (3%) | 13 (4%) | 0 | 5 (1%) |
| Hypophosphataemia | 2 (3%) | 2 (3%) | 0 | 6 (2%) | 4 (1%) | 0 |
| Dehydration | 2 (3%) | 0 | 0 | 5 (1%) | 2 (1%) | 0 |
| Diplopia | 1 (2%) | 1 (2%) | 0 | 4 (1%) | 1 (<1%) | 0 |
| Hypotension | 1 (2%) | 1 (2%) | 0 | 14 (4%) | 2 (1%) | 0 |
| Pyrexia | 1 (2%) | 0 | 0 | 7 (2%) | 1 (<1%) | 0 |
| Lymphocyte count decreased | 1 (2%) | 0 | 0 | 4 (1%) | 1 (<1%) | 0 |
| Pruritus | 1 (2%) | 0 | 0 | 15 (4%) | 1 (<1%) | 0 |
| Hypoxia | 1 (2%) | 0 | 0 | 1 (<1%) | 1 (<1%) | 0 |
| Fall | 1 (2%) | 0 | 0 | 6 (2%) | 1 (<1%) | 0 |
| Osteoarthritis | 0 | 1 (2%) | 0 | 2 (1%) | 1 (<1%) | 0 |
| Blood uric acid increased | 0 | 0 | 1 (2%) | 3 (<1%) | 0 | 1 (<1%) |
| Dysarthria | 0 | 0 | 0 | 5 (1%) | 2 (1%) | 0 |
| Anorectal disorder | 0 | 0 | 0 | 0 | 0 | 1 (<1%) |
| Generalised oedema | 0 | 0 | 0 | 5 (1%) | 2 (1%) | 0 |
| Electrocardiogram QT prolonged | 0 | 0 | 0 | 5 (1%) | 1 (<1%) | 0 |
| Lipase increased | 0 | 0 | 0 | 2 (1%) | 2 (<1%) | 1 (1%) |
| Amylase increased | 0 | 0 | 0 | 1 (<1%) | 3 (1%) | 0 |
| Blood creatine phosphokinase increased | 0 | 0 | 0 | 2 (<1%) | 1 (<1%) | 1 (<1%) |
| Hyponatraemia | 0 | 0 | 0 | 3 (1%) | 2 (1%) | 0 |
| Hypermagnesaemia | 0 | 1 (2%) | 0 | 0 | 1 (<1%) | 0 |
| Hypoalbunimaemia | 0 | 0 | 0 | 0 | 1 (<1%) | 0 |
| Pulmonary oedema | 0 | 0 | 0 | 0 | 2 (1%) | 0 |
| Mental status changes | 0 | 0 | 0 | 0 | 2 (1%) | 0 |
| Agitation | 0 | 0 | 0 | 0 | 1 (<1%) | 0 |
| Mood altered | 0 | 0 | 0 | 0 | 1 (<1%) | 0 |
| Orthostatic hypotension | 0 | 0 | 0 | 2 (1%) | 1 (<1%) | 0 |
| Hypertension | 0 | 0 | 0 | 0 | 1 (<1%) | 0 |
| Cardiac failure | 0 | 1 (2%) | 0 | 0 | 2 (1%) | 0 |
| Cardiac failure congestive | 0 | 1 (2%) | 0 | 0 | 1 (1%) | 0 |
| Myocarditis | 0 | 0 | 0 | 0 | 0 | 1 (<1%) |
Data are n (%). Adverse events were encoded using MedDRA (version 21.0). ALT=alanine aminotransferase. AST=aspartate aminotransferase.
*
All patients with NTRK gene fusions who received ≥1 dose of entrectinib, regardless of dose or duration of follow-up.
†
All patients from STARTRK-1, STARTRK-2, ALKA-372–001, and STARTRK-NG (regardless of tumour type or gene rearrangement) who received ≥1 dose of entrectinib.No deaths due to adverse events were reported.