Table 2.
Treatment-related adverse events, occurring in >10% of patients.
| Dose-level −1 (n = 4) | Dose-level 1 (n = 6) | Dose-level 2 (n = 6) | Dose-level 3 (n = 3) | Dose-level 4 (n = 3) | Dose-level 5 (n = 8) | Dose-level 6 (n = 3) | Dose-level 7 (n = 3) | Dose-level 8 (n = 5) | Total (n = 41) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dacomitinib QD PD-0325901 BID | 15 mg 2 mg |
30 mg 2 mg |
15 mg 3 mg |
15 mg 4 mg |
15 mg 5 mg |
15 mg 6 mg |
30 mg (4/3) 6 mg |
30 mg (5/2) 6 mg (5/2) |
30 mg (5/2) 5 mg (5/2) |
All dose levels | |||||||||
| Adverse event, n (%) | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | Gr 1/2 | Gr 3 | |
| Any skin toxicitya | 3 (7%) | 5 (12%) | 1 (2%) | 6 (15%) | 3 (7%) | 3 (7%) | 5 (12%) | 1 (2%) | 3 (7%) | 3 (7%) | 4 (10%) | 37 (90%) | |||||||
| Rash | 3 (7%) | 5 (12%) | 1 (2%) | 6 (15%) | 3 (7%) | 3 (7%) | 4 (10%) | 1 (2%) | 3 (7%) | 2 ((5%) | 4 (10%) | 35 (85%) | |||||||
| Dry skin | 3 (7%) | 1 (2%) | 2 (5%) | 1 (2%) | 1 (2%) | 1 (2%) | 9 (22%) | ||||||||||||
| Skin fissures | 2 (5%) | 2 (5%) | 4 (10%) | ||||||||||||||||
| PPE | 1 (2%) | 1 (2%) | 1 (2%) | 1 (2%) | 2 (5%) | 6 (15%) | |||||||||||||
| Diarrhoea | 4 (10%) | 6 (15%) | 2 (5%) | 4 (10%) | 1 (2%) | 1 (2%) | 2 (5%) | 4 (10%) | 3 (7%) | 1 (2%) | 1 (2%) | 3 (7%) | 3 (7%) | 1 (2%) | 36 (88%) | ||||
| Nausea | 4 (10%) | 2 (5%) | 1 (2%) | 1 (2%) | 1 (2%) | 2 (5%) | 2 (5%) | 1 (2%) | 5 (12%) | 1 (2%) | 2 (5%) | 3 (7%) | 1 (2%) | 26 (63%) | |||||
| Vomiting | 3 (7%) | 2 (5%) | 1 (2%) | 1 (2%) | 2 (5%) | 1 (2%) | 5 (12%) | 1 (2%) | 1 (2%) | 17 (41%) | |||||||||
| Fatigue | 1 (2%) | 3 (7%) | 1 (2%) | 1 (2%) | 1 (2%) | 1 (2%) | 3 (7%) | 1 (2%) | 1 (2%) | 1 (2%) | 14 (34%) | ||||||||
| Anorexia | 1 (2%) | 3 (7%) | 1 (2%) | 1 (2%) | 1 (2%) | 3 (7%) | 2 (5%) | 12 (29%) | |||||||||||
| CPK increased | 1 (2%) | 1 (2%) | 2 (5%) | 1 (2%) | 1 (2%) | 2 (5%) | 2 (5%) | 10 (24%) | |||||||||||
| ALT/AST increased | 3 (7%) | 1 (2%) | 1 (2%) | 1 (2%) | 1 (2%) | 1 (2%) | 1 (2%) | 9 (22%) | |||||||||||
| Mucositis | 2 (5%) | 1 (2%) | 1 (2%) | 1 (2%) | 2 (5%) | 2 (5%) | 2 (5%) | 11 (27%) | |||||||||||
| Eye toxicityb | 3 (7%) | 1 (2%) | 2 (5%) | 2 (5%) | 8 (20%) | ||||||||||||||
| Alopecia | 3 (7%) | 1 (2%) | 1 (2%) | 1 (2%) | 5 (12%) | ||||||||||||||
| Dry mouth | 2 (5%) | 1 (2%) | 1 (2%) | 1 (2%) | 1 (2%) | 5 (12%) | |||||||||||||
All adverse events that are possible, probable or definite related to study drug were considered as study treatment related.
QD once daily, BID twice daily, ALT/AST alanine/aspartate transaminase, 4/3 4 days on/3 days off, 5/2 5 days on/2 days off, CPK creatine phosphokinase, PPE palmar plantar dysthesia syndrome.
aSome patients experienced one or more skin toxicities; only one was counted for the combined group of any toxicity.
bIncludes neurosensory detachment, blurred vision, retinopathy, cataract and dry eyes.