Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma
Abstract
:1. Introduction
2. Epidemiology
3. BRAF Mutation Testing
4. Clinical and Dermatological Features
5. Biological Identity of Melanoma V600K
6. Therapeutic Effects of BRAF/MEK Inhibitors and Immunotherapy on Melanoma V600K
7. Discussion
8. Conclusions
Author/Year | Country | Ethnicity | n. Patients | n. BRAF Mutated | n. V600K (%) | Sex (M/F) and Age a (Years) | Site and Number of Primary Lesion a | High CSD Number of Patients (%) a |
---|---|---|---|---|---|---|---|---|
Jin SA et al., 2013 [36] | Korea | Asian | 202 | 24 (12%) | 2 (8%) | M, 72 M, 76 | Scalp, 2 (100%) | 1 (50%) |
Lyle et al., 2016 [35] | Australia | Caucasian | 713 | 269 (38%) | 35 (22%) | -M/F ratio from 1.6 to 2.7 c -median age from 60 to 69 c | - b | - b |
Menzies et al., 2012 [10] | Australia | Caucasian | 308 | 143 (46%) | 27 (19%) | -Sex e -median age 61 | -Extremity, 3 (11%) -Trunk, 11 (41%) -Head and neck, 9 (33%) | 12 (75%) |
Si L. et al., 2012 [37] | China | Asian | 438 | 110 (25.5%) | 3 (2.7%) | - b | -b | 0 |
Can et al., 2018 [12] | Turkey | Turkish | 61 | 34 (55.7%) | 11 (32.4%) (M 6, F 5) | -median age 74 | -Extremity, 1 (20.0%) -Head and neck, 6 (54.4%) | - b |
Sakaizawa et al., 2015 [6] | Japan | Asian | 171 | 52 (30.4%) | 3 (5.8%) | - d | - d | 1 (33%) |
Sanna et al., 2020 [14] | Sweden | - b | 72 | 35 (49%) | 7 (20%) | - d | -Head and neck/shoulder region or hands and feet, 4 | 4 (57) |
Study | Treatment | Stage AJCC 8th Ed. | n. BRAF Mutated (%) | n. V600K (%) | OS for All Patients (%/Months) † | PFS for All Patients (%, Months) † | OS for Melanoma V600K Subgroup § | PFS for Melanoma V600K Subgroup § |
---|---|---|---|---|---|---|---|---|
COMBI − d + COMBI v, 2019 [26] | dabrafenib + trametinib | IIIC-IV | 563 (100) | 69 (12) | -5Y-OS 34%, 25.9 months | -dabrafenib + trametinib 5Y-PFS: 19%, 11.1 months | V600E vs. V600K HR 0.77 (0.55–1.06) a | V600E vs. V600K HR 0.65 (0.49–0.87) a |
COLUMBUS, 2018 [28,29] | - encorafenib + binimetinib - encorafenib only agent - vemurafenib only agent | IIIB-C IV | 577 (100) | -encorafenib + binimetinib: 22 (11) -encorafenib only agent: 19 (10) -vemurafenib only agent: 23 (12) | -Encorafenib + Binimetinib: OS 33.6 months (2y-OS 57.6%) -Encorafenib only agent: OS 23.5 months (2y-OS 49.1%) -Vemurafenib only agent: OS 16.9 months (2y -OS 43.2%) | -encorafenib + binmetinib PFS: 14.9 months -encorafenib only agent PFS: 9.6 months -vemurafenib only agent PFS: 7.3 months | Encorafenib + binimetinib vs. vemurafenib only agent HR for OS in V600K subgroup 0.31 (0.13–0.74) b | Encorafenib + binimetinib vs. vemurafenib only agent HR for PFS in V600K subgroup 0.27 (0.11–0.68) b |
coBRIM, 2016 [27] | -cobimetinib + vemurafenib (Arm 1) -vemurafenib + placebo (Arm 2) | IIIC-IV | 495 (100) | Arm 1. 32 (12) Arm 2. 24 (10) | -cobimetinib + verurafenib 22.3 months (2y-OS 48.3%) -vemurafenib + placebo 17.4 months (2y-OS 38.0%) | -cobimetinib + vemurafenib PFS: 12.3 months -vemurafenib + placebo PFS: 7.2 months | median OS cobimetinib + vemurafenib in V600K: 24.1. months median OS placebo + vemurafenib in V600K: 16.7 months HR V600K median OS cobimetinib + vemurafenib vs. placebo + vemurafenib: 0.79 (0.37–1.69) c | median PFS cobimetinib + vemurafenib in V600K: 12.4 months median PFS placebo + vemurafenib in V600K: 6 months HR V600K median PFS cobimetinib + vemurafenib vs. placebo + vemurafenib: 0,52 (0.27–1.02) c |
KEYNOTE 006, 2017 [30] | -pembrolizumab every 3 weeks -pembrolizumab every 2 weeks -ipilimumab | III-IV | 307 (37) | - d | pembrolizumab every 3 weeks 2Y-OS: 55% -pembrolizumab every 2 weeks 2Y-PFS: 55% -ipilimumab 2Y-PFS: 43% | -pembrolizumab every 3 weeks 2Y- PFS: 28% -pembrolizumab every 2 weeks 2Y-PFS: 31% -ipilimumab 2Y-PFS: 14% | - d | - d |
CHECKMATE 067, 2019 [31] | -nivolumab plus ipilimumab -nivolumab alone (N alone) -ipilimumab alone (I alone) | IIIC-IV | 298 (31) | - d | -nivolumab plus ipilimumab 5Y-OS: 52% -nivolumab 5Y-OS: 44% -ipilimumab 5Y-OS: 26% | -nivolumab + ipilimumab 5Y-PFS: 36% -nivolumab 5Y-PFS: 29% -ipilimumab 5Y-PFS: 8% | BRAF mutated vs. WT in nivolumab+ ipilimumab 5y-OS 60% vs. 48% e | BRAF mutated vs. WT in nivolumab+ ipilimumab 5y-PFS 38% vs. 35% e |
KEYNOTE 022, 2020 [32] | -pembrolizumab with dabrafenib and trametinib -placebo with dabrafenib and trametinib | IIIC-IV | 120 (100) | 19 (16) | -pembrolizumab with dabrafenib and trametinib 2Y-OS: 63% -placebo with dabrafenib and trametinib 2Y-OS: 51.7% | -pembrolizumab with dabrafenib and trametinib 2Y-PFS: 41% -placebo with dabrafenib and trametinib 2Y-PFS: 16.3% | - d | - d |
IMspire150, 2020 [33] | -atezolizumab, vemurafenib, and cobimetinib -placebo, vemurafenib, and cobimetinib | IIIC-IV | 514 (100) | 56 (9) | atezolizumab, vemurafenib, and cobimetinib: 2Y-OS 60.4% (median 28.8 months) f -placebo, vemurafenib, and cobimetinib: 2Y-OS 53.1% (median 25.1 months) f | PFS atezolizumab, vemurafenib, and cobimetinib:15.1 months g PFS placebo, vemurafenib, and cobimetinib: 10.6 months g | - d | - d |
Inês Pires da Silva et al., 2013 [24] | -V600K vs. V600E treated with BRAFi ± MEKi h (cohort 1) -V600K vs. V600E treated with Nivolumab or Pembrolizumab (cohort 2) | IIIC-IV | BRAFi +MEKi: 93 (100) Nivolumab/Pembrolizumab:103 (100) | BRAFi ± MEKi: 15 (16) Nivolumab/Pembrolizumab: 19 (18) | - d | - d | BRAFi ± MEKi: V600E 20 months vs. V600K 18 months p 0.87 Nivolumab/pembrolizumab: V600K 20.4 months vs. V600E 11.7 months | BRAFi ± MEKi: V600K 5.7 months vs. V600E 7.1 months p 0.15 Nivolumab/pembrolizumab: V600K 19 months vs. V600E 2.7 months |
RELATIVITY-047 [34] | -Relatlimab + Nivolumab -Nivolumab single agent | III unresectable- IV | 275 (38.5) | - d | - d | Relatlimab + Nivolumab 1y-PFS 47.7%, 10.1 months h Nivolumab single agent 1-PFS 36,0%, 4.6 months h | - d | BRAF mutated vs. WT: no differences for both arms. |
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Nepote, A.; Avallone, G.; Ribero, S.; Cavallo, F.; Roccuzzo, G.; Mastorino, L.; Conforti, C.; Paruzzo, L.; Poletto, S.; Carnevale Schianca, F.; et al. Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma. J. Clin. Med. 2022, 11, 828. https://doi.org/10.3390/jcm11030828
Nepote A, Avallone G, Ribero S, Cavallo F, Roccuzzo G, Mastorino L, Conforti C, Paruzzo L, Poletto S, Carnevale Schianca F, et al. Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma. Journal of Clinical Medicine. 2022; 11(3):828. https://doi.org/10.3390/jcm11030828
Chicago/Turabian StyleNepote, Alessandro, Gianluca Avallone, Simone Ribero, Francesco Cavallo, Gabriele Roccuzzo, Luca Mastorino, Claudio Conforti, Luca Paruzzo, Stefano Poletto, Fabrizio Carnevale Schianca, and et al. 2022. "Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma" Journal of Clinical Medicine 11, no. 3: 828. https://doi.org/10.3390/jcm11030828
APA StyleNepote, A., Avallone, G., Ribero, S., Cavallo, F., Roccuzzo, G., Mastorino, L., Conforti, C., Paruzzo, L., Poletto, S., Carnevale Schianca, F., Quaglino, P., & Aglietta, M. (2022). Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma. Journal of Clinical Medicine, 11(3), 828. https://doi.org/10.3390/jcm11030828