Optimal Use of BRAF Targeting Therapy in the Immunotherapy Era

Curr Oncol Rep. 2016 Nov;18(11):67. doi: 10.1007/s11912-016-0554-5.

Abstract

Purpose of review: The therapeutic landscape for metastatic melanoma has been revolutionized in recent years. This review will discuss existing evidence for therapeutic approaches for BRAF-mutated metastatic melanoma.

Recent findings: Clinical trials involving combined BRAF/MEK inhibition with either vemurafenib plus cobimetinib or dabrafenib plus trametinib have shown improved overall survival compared to monotherapy with BRAF inhibitors alone. In a subset of patients with good prognostic factors, long-term clinical benefit has been noted. Simultaneously, developments in immunotherapy have suggested long-lasting survival for some patients. In advanced BRAF-mutated melanoma, both BRAF/MEK inhibition and immunotherapy agents show improved overall survival and, in a small population of patients, prolonged and long-term benefit as compared to standard chemotherapy. Trials are currently underway evaluating sequencing of these therapies and the safety of targeted therapy plus immunotherapy combinations.

Keywords: BRAF; Dabrafenib; Immunotherapy; MEK; Melanoma; Metastatic; Vemurafenib.

Publication types

  • Review

MeSH terms

  • Combined Modality Therapy
  • Humans
  • Immunomodulation / drug effects*
  • Immunomodulation / genetics
  • Immunotherapy*
  • Melanoma / genetics
  • Melanoma / immunology*
  • Melanoma / therapy*
  • Mutation / genetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics

Substances

  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf