Table 2.
Adverse events and effect on further treatment, reported per treatment cohort
| Adverse event | Cohort 1 (n=8) PEM |
Cohort 2 (n=8) PEM + 2×1W D+T |
Cohort 3 (n=8) PEM + 2×2W D+T |
Cohort 4 (n=8) PEM + 6W D+T |
||||||||||||
| All grades | Grade 3–4 | All grades | Grade 3–4 | All grades | Grade 3–4 | All grades | Grade 3–4 | |||||||||
| Any adverse event | 7 | (88) | 1 | (12) | 8 | (100) | 1 | (12) | 8 | (100) | 4 | (50) | 8 | (100) | 5 | (63) |
| Fatigue | 4 | (50) | 6 | (75) | 7 | (88) | 7 | (88) | ||||||||
| Headache | 1 | (12) | 3 | (38) | 3 | (38) | 1 | (12) | 6 | (75) | ||||||
| Fever | 1 | (12) | 5 | (62) | 1 | (12) | 6 | (75) | 1 | (12) | ||||||
| ALT increased | 1 | (12) | 5 | (62) | 5 | (62) | 3 | (38) | ||||||||
| Influenza like symptoms | 4 | (50) | 3 | (38) | 1 | (12) | 4 | (50) | ||||||||
| Rash | 2 | (25) | 1 | (12) | 1 | (12) | 2 | (25) | 1 | (12) | 5 | (62) | 1 | (12) | ||
| AST increased | 5 | (62) | 5 | (62) | 4 | (50) | ||||||||||
| Arthralgia | 1 | (12) | 4 | (50) | 5 | (62) | ||||||||||
| Pruritus | 2 | (25) | 3 | (38) | 2 | (25) | 4 | (50) | ||||||||
| Nausea | 3 | (38) | 3 | (38) | 3 | (38) | ||||||||||
| Myalgia | 1 | (12) | 4 | (50) | 1 | (12) | 2 | (25) | 1 | (12) | ||||||
| Diarrhea | 4 | (50) | 2 | (25) | 2 | (25) | ||||||||||
| Neutrophil count decreased | 2 | (25) | 2 | (25) | 2 | (25) | 1 | (12) | ||||||||
| Hypothyroidism | 1 | (12) | 2 | (25) | 3 | (38) | ||||||||||
| Vomiting | 1 | (12) | 2 | (25) | 3 | (38) | ||||||||||
| Dry mouth | 1 | (12) | 3 | (38) | 2 | (25) | ||||||||||
| Dysgeusia | 1 | (12) | 2 | (25) | 2 | (25) | ||||||||||
| Hyperthyroidism | 1 | (12) | 2 | (25) | 2 | (25) | ||||||||||
| Skin hypopigmentation | 2 | (25) | 1 | (12) | 2 | (25) | ||||||||||
| Mucositis oral | 1 | (12) | 1 | (12) | 1 | (12) | ||||||||||
| Pancreatitis | 1 | (12) | 1 | (12) | ||||||||||||
|
Cohort 1
PEM |
Cohort 2
PEM + 2×1W D+T |
Cohort 3
PEM + 2×2W D+T |
Cohort 4
PEM + 6W D+T |
|||||||||||||
| Led to interruption of D+T | NA | – | – | 1 (12) | ||||||||||||
| Led to discontinuation of D+T | NA | 1 (12) | 3 (38) | 4 (50) | ||||||||||||
| Led to interruption of PEM | 1 (12) | – | 3 (38) | 5 (63) | ||||||||||||
| Led to discontinuation of PEM | – | 1 (12) | 2 (25) | – | ||||||||||||
| Treatment with steroids | ||||||||||||||||
| <1 mg/kg | 2 (25) | 2 (25) | 2 (25) | 2 (25) | ||||||||||||
| ≥1 mg/kg | – | – | 2 (25) | 4 (50) | ||||||||||||
ALT, alanine aminotransferase; AST, aspartate aminotransferase; D+T, dabrafenib+trametinib; PEM, pembrolizumab; W, weeks.