open access

Vol 13, No 6 (2017)
Review paper
Published online: 2018-01-04
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Treatment of BRAF+ melanoma in light of current drug programs

Piotr Rutkowski, Tomasz Świtaj
DOI: 10.5603/OCP.2017.0036
·
Oncol Clin Pract 2017;13(6):275-280.

open access

Vol 13, No 6 (2017)
REVIEW ARTICLES
Published online: 2018-01-04

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).

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).
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Keywords

melanoma, BRAF, BRAF inhibitor, MEK inhibitor

About this article
Title

Treatment of BRAF+ melanoma in light of current drug programs

Journal

Oncology in Clinical Practice

Issue

Vol 13, No 6 (2017)

Article type

Review paper

Pages

275-280

Published online

2018-01-04

DOI

10.5603/OCP.2017.0036

Bibliographic record

Oncol Clin Pract 2017;13(6):275-280.

Keywords

melanoma
BRAF
BRAF inhibitor
MEK inhibitor

Authors

Piotr Rutkowski
Tomasz Świtaj

References (38)
  1. Rutkowski P. Złośliwe nowotwory skóry. Wyd. 2. Via Medica, Gdańsk 2014.
  2. Rutkowski P, Wysocki PJ, Nasierowska-Guttmejer A, et al. Cutaneous melanoma — diagnostic and therapeutic guidelines in 2016. Oncol Clin Pract. 2015; 11: 216–231.
  3. Wojciechowska U, Olasek P, Czauderna K, et al. Nowotwory złośliwe w Polsce w 2014 roku. Cancer in Poland in 2014. Ministerstwo Zdrowia Warszawa. ; 2016.
  4. 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.
  5. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002; 417(6892): 949–954.
  6. 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.
  7. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005; 353(20): 2135–2147.
  8. Garrido MC, Bastian BC. KIT as a therapeutic target in melanoma. J Invest Dermatol. 2010; 130(1): 20–27.
  9. 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.
  10. 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.
  11. 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.
  12. Gray-Schopfer VC, da Rocha Dias S, Marais R. The role of B-RAF in melanoma. Cancer Metastasis Rev. 2005; 24(1): 165–183.
  13. Wellbrock C, Hurlstone A. BRAF as therapeutic target in melanoma. Biochem Pharmacol. 2010; 80(5): 561–567.
  14. Maldonado JL, Fridlyand J, Patel H, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. 2003; 95(24): 1878–1890.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. Smalley KSM. A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? Int J Cancer. 2003; 104(5): 527–532.
  20. Michaloglou C, Vredeveld LCW, Soengas MS, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005; 436(7051): 720–724.
  21. Chin L, Garraway LA, Fisher DE. Malignant melanoma: genetics and therapeutics in the genomic era. Genes Dev. 2006; 20(16): 2149–2182.
  22. Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003; 33(1): 19–20.
  23. Miller A, Mihm M. Melanoma. N Engl J Med. 2006; 355(1): 51–65.
  24. Rutkowski P. Nowe terapie w czerniakach. Via Medica (2 wydanie), Gdańsk 2017.
  25. NCCN Clinical Practice Guidelines in Oncology.Melanoma v. 1. 2016.
  26. 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.
  27. 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.
  28. 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).
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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).
  34. Koseła-Paterczyk H. Polskie wyniki programów lekowych z przeciwciałami anty-PD-1 oraz inhibitorami BRAF+MEK.Warsaw Skin Cancer Conference 2017.
  35. 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.
  36. 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.
  37. 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.
  38. 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.

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