Table 1.

Summary of BRAF, MEK1/2 mutation status, and patient characteristics

Study sitePatient numberBRAF exon 15 baselineMEK1 exon 3 baselineMEK2 exon 3 baselineMEK1 exon 3 at progressive diseaseAge and genderStageDose of BRAFi (mg)Best overall responseProgression-free survival (days)Sites of baseline tumors biopsiedaResponses of baseline tumors biopsieda
UCLA1V600EWTWTWT
WT
WT
65 FM1c1120 bid−37%279
2V600EP124SWTP124S46 MM1c960 bid−32%149Axillary nodeDay 15 PET uptake decrease (Fig. 1A)
3V600EWTWTWT
WT
WT
66 FM1b960 bid−53%137
4V600EWTWTWT
WT
48 MM1c960 bid−24%126
5V600EWTWTWT54 MM1c960 bid−75%84
6V600EWTWTWT
WT
65 FM1c960 bid−72%373
7V600EWTWTWT
WT
51 MM1c960 bid−60%212
8V600EWTWTWT47 FM1b960 bid−72%97
9bV600EWTWTWT
WT
WT
47 FIIIc150 bid−31%238
10V600EWTWTDP N/A52 MM1c960 bid−70%
11V600KP124SWTDP N/A72 FM1c960 bid−11%80Axillary nodeDecrease by 25% in longest tumor dimension
12bV600EP124SWTDP N/A48 FM1c150 bid−9%104Axillary nodeNot palpable (Fig. 1B)
13V600KWTWTDP N/A66 MM1c960 bid−30%140
14V600EWTWTDP N/A57 MM1c960 bid−47%189
15V600EWTWTDP N/A55 MM1c960 bid−50%300
16V600EWTWTResponding53 FM1a960 bid−91.7%
17V600EWTWTResponding45 FM1c960 bid−73%
18V600EWTWTDP N/A29 FM1c960 bid−34.5%289
19V600EWTWTResponding74 MIIIc960 bid−20%
20V600KWTWTWT65 MM1c960 bid−22%161
21V600KWTWTResponding61 MM1c960 bid−34%
22V600EWTWTResponding60 FM1a960 bid−42%
23bV600EWTWTDP N/A36 FM1c150 bid−66%85
24bV600EWTWTDP N/A65 FM1c150 bid−39.5%76
MIA25bV600KWTWTWT59 MM1c100 bid, dose escalated to 100 tid−14%224
26V600EWTWTWT71 MM1c960 bid−53%239
27bV600KI111SWTI111S
I111S
38 FM1a35 bid, dose escalated to 100 tid 18 Dec 2009−100%119Right inguinal nodeDay 15 PET uptake decrease in single measurable lesion
28bV600KP124SWTP124S39 MM1c150 bid−56%118Right neck nodeDay 15 PET uptake decrease (regional, Fig. 1C); SUV max reduced 48% overall metastases
29bWTWTWT58 FM1c70 bid, dose escalated to 100 tid 29 Dec 2009−63%209
VI30V600EWTWTWT46 FM1c720−59%107
31V600EWTWTWT70 FM1a960−70%183
  • NOTE: Highlighting, information for patients whose tumors harbor MEK1 mutations. Dashes, data not applicable.

    Mean progression-free survival for patients with WT MEK1 melanomas = 182.4 days (SD 84.7) versus mutant MEK1 melanomas = 114 days [SD 25.1, (2-tailed P = 0.09)]. Mean best overall response for patients with WT MEK1 melanomas = −50% (SD 20.0) versus mutant MEK1 melanomas = 41.6 [SD 37.8, 2-tailed P = 0.45)]. Partial response (PR) for patients with WT MEK1 melanomas (21/26 or 80%) versus mutant MEK1 melanomas (3/5 or 60%).

    Abbreviations: bid, twice a day; DP, disease progression; MIA, Melanoma Institute, Australia; PET, positron emission tomography; SUVmax, maximum standard uptake value; tid, 3 times a day; UCLA, University of California, Los Angeles; VI, Vanderbilt-Ingram Cancer Center

  • a Information only for applicable patients with MEK1-mutant melanomas.

  • b Dabrafenib-treated patients. All others were treated with vemurafenib.