Vol 13, No 6 (2017)
Review paper
Published online: 2018-01-04
Treatment of BRAF+ melanoma in light of current drug programs
DOI: 10.5603/OCP.2017.0036
Oncol Clin Pract 2017;13(6):275-280.
Abstract
The past decade has seen significant advances in the understanding of molecular pathogenesis of cutaneous melanoma. Currently, mutations of BRAF oncogene have been a well established and powerful predictive role as validated target in recently developed molecular targeted therapy for melanoma. It has been proven in a number of studies that the effective treatment for this group of patients consists of the combination of a BRAF inhibitor and MEK inhibitor, two such combinations are currently registered and reimbursed in Poland — vemurafenib and cobimetinib, dabrafenib and trametinib. Median progression-free survival (PFS) exceeds one year for BRAF and MEK combined therapy, and overall survival (OS) reaches approximately 2 years. Currently, the first line therapeutic option for BRAF-mutated advanced melanoma include also immunotherapy with anti-PD-1 antibodies (combination of PD-1/CTLA-4 blockers can be an option in a specific group of patients, although not reimbursed in Poland).
Keywords: melanomaBRAFBRAF inhibitorMEK inhibitor
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- Rutkowski P. Złośliwe nowotwory skóry. Wyd. 2. Via Medica, Gdańsk 2014.
- Rutkowski P, Wysocki PJ, Nasierowska-Guttmejer A, et al. Cutaneous melanoma — diagnostic and therapeutic guidelines in 2016. Oncol Clin Pract. 2015; 11: 216–231.
- Wojciechowska U, Olasek P, Czauderna K, et al. Nowotwory złośliwe w Polsce w 2014 roku. Cancer in Poland in 2014. Ministerstwo Zdrowia Warszawa. ; 2016.
- Hocker TL, Singh MK, Tsao H. Melanoma genetics and therapeutic approaches in the 21st century: moving from the benchside to the bedside. J Invest Dermatol. 2008; 128(11): 2575–2595.
- Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002; 417(6892): 949–954.
- Curtin JA, Busam K, Pinkel D, et al. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006; 24(26): 4340–4346.
- Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005; 353(20): 2135–2147.
- Garrido MC, Bastian BC. KIT as a therapeutic target in melanoma. J Invest Dermatol. 2010; 130(1): 20–27.
- Kumar R, Angelini S, Snellman E, et al. BRAF mutations are common somatic events in melanocytic nevi. J Invest Dermatol. 2004; 122(2): 342–348.
- Platz A, Egyhazi S, Ringborg U, et al. Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site. Mol Oncol. 2008; 1(4): 395–405.
- Satyamoorthy K, Li G, Gerrero MR, et al. Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res. 2003; 63(4): 756–759.
- Gray-Schopfer VC, da Rocha Dias S, Marais R. The role of B-RAF in melanoma. Cancer Metastasis Rev. 2005; 24(1): 165–183.
- Wellbrock C, Hurlstone A. BRAF as therapeutic target in melanoma. Biochem Pharmacol. 2010; 80(5): 561–567.
- Maldonado JL, Fridlyand J, Patel H, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. 2003; 95(24): 1878–1890.
- Rubinstein JC, Sznol M, Pavlick AC, et al. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J Transl Med. 2010; 8: 67.
- Jewell R, Chambers P, Harland M, et al. Clinicopathologic features of V600E and V600K melanoma--letter. Clin Cancer Res. 2012; 18(24): 6792; author's reply p. 6793.
- Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011; 29(10): 1239–1246.
- Sharma A, Trivedi NR, Zimmerman MA, et al. Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res. 2005; 65(6): 2412–2421.
- Smalley KSM. A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? Int J Cancer. 2003; 104(5): 527–532.
- Michaloglou C, Vredeveld LCW, Soengas MS, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005; 436(7051): 720–724.
- Chin L, Garraway LA, Fisher DE. Malignant melanoma: genetics and therapeutics in the genomic era. Genes Dev. 2006; 20(16): 2149–2182.
- Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003; 33(1): 19–20.
- Miller A, Mihm M. Melanoma. N Engl J Med. 2006; 355(1): 51–65.
- Rutkowski P. Nowe terapie w czerniakach. Via Medica (2 wydanie), Gdańsk 2017.
- NCCN Clinical Practice Guidelines in Oncology.Melanoma v. 1. 2016.
- Ascierto P, McArthur G, Dréno B, et al. Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. The Lancet Oncology. 2016; 17(9): 1248–1260.
- Daud A, Pavlick AC, Ribas A, et al. Extended follow-up results of a phase 1B study (BRIM7) of cobimetinib (C) and vemurafenib (V) in BRAF-mutant melanoma. J Clin Oncol. 2016; 34(supl.): abstract.
- Robert C, Karaszewska B, Schachter J, et al. Three-year estimate of overall survival in COMBI-v, a randomized phase 3 study evaluating first-line dabrafenib (D) + trametinib (T) in patients (pts) with unresectable or metastatic BRAF V600E/K–mutant cutaneous melanoma. Ann Oncol. 2016; 27(suppl_6).
- Long GV, Flaherty KT, Stroyakovskiy D, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol. 2017; 28(7): 1631–1639.
- Schadendorf D, Long GV, Stroiakovski D, et al. Three-year pooled analysis of factors associated with clinical outcomes across dabrafenib and trametinib combination therapy phase 3 randomised trials. Eur J Cancer. 2017; 82: 45–55.
- Sullivan RJ, et al. A phase Ib/II study of BRAF inhibitor (BRAFi) encorafenib (ENCO) plus MEK inhibitor (MEKi) binimetinib (BINI) in cutaneous melanoma patients naive to BRAFi treatment. ASCO 2015, Streszczenie nr. ; 9007.
- Schreuer M, Jansen Y, Planken S, et al. Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Lancet Oncol. 2017; 18(4): 464–472.
- Valpione S, Carlino MS, Mangana J, et al. Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. J Clin Oncol. 2017; 35(suppl; abstr 9512).
- Koseła-Paterczyk H. Polskie wyniki programów lekowych z przeciwciałami anty-PD-1 oraz inhibitorami BRAF+MEK.Warsaw Skin Cancer Conference 2017.
- Long GV, Hauschild A, Santinami M, et al. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med. 2017; 377(19): 1813–1823.
- Robert C, Schachter J, Long GV, et al. KEYNOTE-006 investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015; 372(26): 2521–2532.
- Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015; 372(4): 320–330.
- Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017; 377(14): 1345–1356.