Table 3.
Adverse events: selumetinib in combination with docetaxel or dacarbazine
| Part A | Part B | Part A + B | |||
|---|---|---|---|---|---|
| Selumetinib 50 mg BID (N = 7) | Selumetinib 75 mg BID with ppG-CSF (N = 7) | Selumetinib 75 mg BID without ppG-CSF (N = 8) | Selumetinib 75 mg BIDa (N = 13) | Selumetinib 75 mg BID (N = 28) | |
| Selumetinib in combination with docetaxel AE category, n (%) | |||||
| Any AE | 7 (100.0) | 7 (100.0) | 8 (100.0) | 12 (92.3) | 27 (96.4) |
| Any grade ≥3 AE | 5 (71.4) | 1 (14.3) | 7 (87.5) | 11 (84.6) | 19 (67.9) |
| Any SAE | 4 (57.1) | 2 (28.6) | 5 (62.5) | 7 (53.8) | 14 (50.0) |
| Any AE leading to discontinuation | 0 | 0 | 0 | 2 (15.4) | 2 (7.1) |
| Most frequently reported AEs (≥20% of patients receiving selumetinib 75 mg BID + docetaxel), n (%) | |||||
| Diarrhea | 5 (71.4) | 3 (42.9) | 7 (87.5) | 11 (84.6) | 21 (75.0) |
| Edema peripheral | 5 (71.4) | 3 (42.9) | 7 (87.5) | 10 (76.9) | 20 (71.4) |
| Fatigue | 7 (100.0) | 2 (28.6) | 5 (62.5) | 9 (69.2) | 16 (57.1) |
| Nausea | 2 (28.6) | 3 (42.9) | 4 (50.0) | 8 (61.5) | 15 (53.6) |
| Vomiting | 4 (57.1) | 3 (42.9) | 4 (50.0) | 5 (38.5) | 12 (42.9) |
| Dermatitis acneiform | 3 (42.9) | 4 (57.1) | 3 (37.5) | 5 (38.5) | 12 (42.9) |
| Neutropenia | 4 (57.1) | 1 (14.3) | 5 (62.5) | 5 (38.5) | 11 (39.3) |
| Constipation | 3 (42.9) | 2 (28.6) | 3 (37.5) | 4 (30.8) | 9 (32.1) |
| Dyspnea exertional | 3 (42.9) | 1 (14.3) | 2 (25.0) | 5 (38.5) | 8 (28.6) |
| Epistaxis | 3 (42.9) | 2 (28.6) | 2 (25.0) | 4 (30.8) | 8 (28.6) |
| Dysgeusia | 2 (28.6) | 2 (28.6) | 1 (12.5) | 5 (38.5) | 8 (28.6) |
| Neuropathy peripheral | 2 (28.6) | 2 (28.6) | 3 (37.5) | 3 (23.1) | 8 (28.6) |
| Mucosal inflammation | 5 (71.4) | 3 (42.9) | 1 (12.5) | 2 (15.4) | 6 (21.4) |
| Nail disorder | 1 (14.3) | 1 (14.3) | 3 (37.5) | 2 (15.4) | 6 (21.4) |
| Selumetinib in combination with dacarbazine AE category, n (%) | |||||
| Any AE | 7 (100.0) | 6 (100.0) | 12 (100.0) | 18 (100.0) | |
| Any grade ≥3 | 7 (100.0) | 2 (33.3) | 9 (75.0) | 11 (61.1) | |
| Any SAE | 4 (57.1) | 2 (33.3) | 4 (33.3) | 6 (33.3) | |
| Any AE leading to discontinuation | 0 | 0 | 1 (8.3) | 1 (5.6) | |
| Most frequently reported AEs (≥30% of patients receiving selumetinib 75 mg BID + dacarbazine), n (%) | |||||
| Diarrhea | 4 (57.1) | 6 (100.0) | 9 (75.0) | 15 (83.3) | |
| Nausea | 5 (71.4) | 5 (83.3) | 10 (83.3) | 15 (83.3) | |
| Fatigue | 2 (28.6) | 3 (50.0) | 11 (91.7) | 14 (77.8) | |
| Decreased appetite | 1 (14.3) | 3 (50.0) | 8 (66.7) | 11 (61.1) | |
| Dizziness | 1 (14.3) | 2 (33.3) | 8 (66.7) | 10 (55.6) | |
| Headache | 1 (14.3) | 4 (66.7) | 6 (50.0) | 10 (55.6) | |
| Vomiting | 1 (14.3) | 3 (50.0) | 7 (58.3) | 10 (55.6) | |
| Constipation | 3 (42.9) | 3 (50.0) | 6 (50.0) | 9 (50.0) | |
| Dermatitis acneiform | 1 (14.3) | 2 (33.3) | 7 (58.3) | 9 (50.0) | |
| Edema peripheral | 3 (42.9) | 1 (16.7) | 8 (66.7) | 9 (50.0) | |
| Dyspnea exertional | 1 (14.3) | 2 (33.3) | 6 (50.0) | 8 (44.4) | |
| Asthenia | 0 | 2 (33.3) | 5 (41.7) | 7 (38.9) | |
| Vision blurred | 0 | 1 (16.7) | 6 (50.0) | 7 (38.9) | |
| Periorbital edema | 1 (14.3) | 0 | 6 (50.0) | 6 (33.3) | |
Docetaxel, 75 mg/m2; dacarbazine 1000 mg/m2
appG-CSF allowed from cycle 2 onwards
AE, adverse event; BID, twice daily; ppG-CSF, primary prophylactic granulocyte-colony stimulating factor; SAE, serious adverse event