Table 2.
Adverse Events Reported in Part C.*
| Adverse Event | Dabrafenib Monotherapy (N = 5)† | Combination 150/1 (N = 54) | Combination 150/2 (N = 55)† | |||
|---|---|---|---|---|---|---|
| Grade 3 or 4 | All Grades | Grade 3 or 4 | All Grades | Grade 3 or 4 | All Grades | |
| number of patients (percent) | ||||||
|
| ||||||
| Any event | 23 (43) | 53 (100) | 26 (48) | 53 (98) | 32 (58) | 55 (100) |
|
| ||||||
| Pyrexia | 0 | 14 (26) | 5 (9) | 37 (69) | 3 (5) | 39 (71) |
|
| ||||||
| Chills | 0 | 9 (17) | 1 (2) | 27 (50) | 1 (2) | 32 (58) |
|
| ||||||
| Fatigue | 3 (6) | 21 (40) | 1 (2) | 31 (57) | 2 (4) | 29 (53) |
|
| ||||||
| Nausea | 0 | 11 (21) | 3 (6) | 25 (46) | 1 (2) | 24 (44) |
|
| ||||||
| Vomiting | 0 | 8 (15) | 2 (4) | 23 (43) | 1 (2) | 22 (40) |
|
| ||||||
| Diarrhea | 0 | 15 (28) | 0 | 14 (26) | 1 (2) | 20 (36) |
|
| ||||||
| Headache | 0 | 15 (28) | 1 (2) | 20 (37) | 0 | 16 (29) |
|
| ||||||
| Peripheral edema | 0 | 9 (17) | 0 | 13 (24) | 0 | 16 (29) |
|
| ||||||
| Cough | 0 | 11 (21) | 0 | 6 (11) | 0 | 16 (29) |
|
| ||||||
| Arthralgia | 0 | 18 (34) | 0 | 24 (44) | 0 | 15 (27) |
|
| ||||||
| Rash | 0 | 19 (36) | 0 | 11 (20) | 0 | 15 (27) |
|
| ||||||
| Night sweats | 0 | 3 (6) | 0 | 8 (15) | 0 | 13 (24) |
|
| ||||||
| Decreased appetite | 0 | 10 (19) | 0 | 16 (30) | 0 | 12 (22) |
|
| ||||||
| Myalgia | 1 (2) | 12 (23) | 0 | 13 (24) | 1 (2) | 12 (22) |
|
| ||||||
| Constipation | 0 | 6 (11) | 1 (2) | 9 (17) | 0 | 12 (22) |
|
| ||||||
| Elevated blood alkaline phosphatase | 0 | 1 (2) | 3 (6) | 12 (22) | 0 | 5 (9) |
|
| ||||||
| Hyperkeratosis | 0 | 16 (30) | 0 | 3 (6) | 0 | 5 (9) |
|
| ||||||
| Alopecia | 0 | 18 (34) | 0 | 5 (9) | 0 | 3 (5) |
|
| ||||||
| Grade 3‡ | All Grades | Grade 3‡ | All Grades | Grade 3‡ | All Grades | |
|
| ||||||
| Cutaneous squamous-cell carcinoma§ | 9 (17) | 10 (19) | 1 (2) | 1 (2) | 3 (5) | 4 (7) |
|
| ||||||
| Skin papilloma | 0 | 8 (15) | 0 | 4 (7) | 0 | 2 (4) |
|
| ||||||
| Hyperkeratosis | 0 | 16 (30) | 0 | 3 (6) | 0 | 5 (9) |
|
| ||||||
| Decreased ejection fraction | 0 | 0 | 1 (2) | 2 (4) | 0 | 5 (9) |
|
| ||||||
| Cardiac failure | 0 | 0 | 1 (2) | 1 (2) | 0 | 0 |
|
| ||||||
| Hypertension | 0 | 2 (4) | 0 | 2 (4) | 1 (2) | 5 (9) |
|
| ||||||
| Chorioretinopathy | 0 | 0 | 0 | 0 | 1 (2) | 1 (2) |
Listed are all adverse events that were reported in more than 20% of patients in any group, regardless of whether a causal relationship was likely. In addition to these events, there was one death from sepsis in the combination 150/1 group and there were three deaths in the combination 150/2 group (two from brain hemorrhage and one from pulmonary embolism). None of these events were considered to be related to a study drug. Neutropenia (grade 3 or 4) occurred in 11% of patients in the combination 150/2 group, with one case of febrile neutropenia. Acneiform dermatitis occurred in 11% of patients in the combination 150/1 group, 16% in the combination 150/2 group, and 4% in the monotherapy group, with no grade 3 or 4 events reported.
One patient who was assigned to the monotherapy group received combination 150/2 and so was included in the combination 150/2 safety analyses.
For these categories, no grade 4 events were reported.
Keratoacanthoma was classified as cutaneous squamous-cell carcinoma.