Table 1. Patient disposition.
| BRAF-mutant | NRAS-mutant | All patients | ||
|---|---|---|---|---|
| Binimetinib 45 mg (n = 41) |
Binimetinib 60 mg (n = 25) |
Binimetinib 45 mg (n = 117) |
N = 183 | |
| Patients treated, n (%) | ||||
| Treatment discontinued | 41 (100) | 23 (92.0) | 104 (88.9) | 168 (91.8) |
| Treatment ongoinga | 0 | 2 (8.0) | 13 (11.1) | 15 (8.2) |
| Primary reason for end of treatment, n (%) | ||||
| Adverse event(s)b | 12 (29.3) | 5 (20.0) | 14 (12.0) | 31 (16.9) |
| Patient withdrew consent | 2 (4.9) | 1 (4.0) | 4 (3.4) | 7 (3.8) |
| Disease progression | 26 (63.4) | 16 (64.0) | 86 (73.5) | 128 (69.9) |
| Protocol deviation | 1 (2.4) | 1 (4.0) | 0 | 2 (1.1) |
| Duration of exposure, median (range), weeks | 9.6 (1.1–26.6) | 8.0 (2.0–102) | 15.9 (0.3–87.9) | 11.6 (0.3–102.0) |
| BRAF mutation status, n (%)c | ||||
| None (no wild-type mutation detected) | 0 | 0 | 3 (2.6) | |
| V600E | 34 (82.9) | 19 (76.0) | 0 | |
| V600K | 5 (12.2) | 1 (4.0) | 0 | – |
| Unknown mutation | 1 (2.4)f | 2 (8.0)f | 0 | |
| Other (mutations other than V600E/K)d | 1 (2.4)g | 0 | 0 | |
| Missing (no V600 BRAF mutation data)e | 0 | 3 (12.0)f | 114 (97.4) | |
| NRAS mutation status, n (%)d | ||||
| None (no mutation detected) | 0 | 5 (20.0) | 4 (3.4)h | |
| Q61 | 0 | 0 | 100 (85.5) | |
| G12/13 | 0 | 0 | 2 (1.7) | – |
| Unknown mutationc | 1 (2.4) | 0 | 1 (0.9)i | |
| Missing (no NRAS mutation data) | 40 (97.6) | 20 (80.0) | 10 (8.5)j | |
| Clinical activityk [24] | (n = 35) | NR | (n = 28) | |
| DCR, n (%) | 21 (60) | NR | 19 (68) | |
aTreatment ongoing at the time of the cut-off (Jan 7, 2014)
bIncludes fatal case with liver failure in the BRAF-mutated 60-mg treatment group;
cAny other mutation not known; known mutation includes all Q61, A59T, A11T, G12V, G13R;
dAny other known mutation (L597, D594, G606, K60);
eAnalysis results are missing;
fV600E according to local laboratory;
gV600R according to local laboratory;
hThree Q61R (1 result received after database lock) and one G12 (result received after database lock);
iQ61R according to local laboratory;
jThree Q61R, two Q61L, two Q61K, two Q61, and one G12 mutation according to local laboratory.
kData for clinical activity available for 63 patients for response-rate analysis set (Ascierto, 2013).
DCR, disease control rate; NR, not reported.