Vol 14, No 1 (2018)
Review paper
Published online: 2018-02-28
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Treatment of patients with advanced melanoma harboring the BRAF V600 mutation

Joanna Połowinczak-Przybyłek, Piotr Potemski
DOI: 10.5603/OCP.2018.0003
Oncol Clin Pract 2018;14(1):48-52.

Abstract

The advances in the treatment of melanoma patients with V600 mutations in the BRAF gene over the past few  years result from the introduction of targeted drugs and modern immunotherapy. Unfortunately, at the moment  there is a lack of data from a randomised clinical trial that determines the optimal sequence of anti-BRAF/anti-MEK  drugs and immunotherapy in BRAF (+) patients. This paper discusses the most important clinical trials performed  so far, the results of which may be helpful in the selection of systemic treatment in patients with advanced or  metastatic melanoma harbouring BRAF V600 mutation. Formal analysis indicates that molecularly targeted treatment  is the method of choice in the first-line setting in patients with BRAF (+) melanoma because the value of  anti-BRAF/anti-MEK drugs in this population was confirmed by consistent results of three phase 3 studies. Conversely,  evidence for the effectiveness of immunotherapy in advanced BRAF (+) melanoma are much weaker.  However, both methods significantly improved the prognosis, and in some patients with BRAF gene mutation they  led to long-term survival. Currently, the research is ongoing, and the results may resolve this issue. 

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References

  1. Queirolo P, Spagnolo F. BRAF plus MEK-targeted drugs: a new standard of treatment for BRAF-mutant advanced melanoma. Cancer Metastasis Rev. 2017; 36(1): 35–42.
  2. 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.
  3. Daud A, Gill J, Kamra S, et al. Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients. J Hematol Oncol. 2017; 10(1): 3.
  4. Ascierto PA, McArthur GA, Dréno B, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016; 17(9): 1248–1260.
  5. 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.
  6. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015; 372(1): 30–39.
  7. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011; 364(26): 2517–2526.
  8. Weber JS, D'Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015; 16(4): 375–384.
  9. Larkin J, Minor D, D'Angelo S, et al. Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial. J Clin Oncol. 2017 [Epub ahead of print]: JCO2016718023.
  10. 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.
  11. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015; 373: 23–34.
  12. Wolchok J, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. New England Journal of Medicine. 2017; 377(14): 1345–1356.
  13. 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.
  14. Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017; 390(10105): 1853–1862.
  15. Ascierto PA, Simeone E, Giannarelli D, et al. Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J Transl Med. 2012; 10: 107.
  16. Ackerman A, Klein O, McDermott DF, et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer. 2014; 120(11): 1695–1701.
  17. Aya F, Fernandez-Martinez A, Gaba L, et al. Sequential treatment with immunotherapy and BRAF inhibitors in BRAF-mutant advanced melanoma. Clin Transl Oncol. 2017; 19(1): 119–124.
  18. Johnson DB, Pectasides E, Feld E, et al. Sequencing Treatment in BRAFV600 Mutant Melanoma: Anti-PD-1 Before and After BRAF Inhibition. J Immunother. 2017; 40(1): 31–35.
  19. Larkin J, Lao CD, Urba WJ, et al. Efficacy and Safety of Nivolumab in Patients With BRAF V600 Mutant and BRAF Wild-Type Advanced Melanoma: A Pooled Analysis of 4 Clinical Trials. JAMA Oncol. 2015; 1(4): 433–440.
  20. Long GV, Atkinson V, Menzies AM, et al. A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases (mets): The Anti-PD1 Brain Collaboration (ABC). JClinOncol 2017;35(15_suppl. ; 9508.
  21. https://clinicaltrials.gov/ct2/show/NCT02224781.
  22. https://clinicaltrials.gov/ct2/show/NCT02631447.