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The Role of BRAF-Targeted Therapy for Advanced Melanoma in the Immunotherapy Era

Current Oncology Reports volume 21, Article number: 76 (2019) Cite this article

Abstract

Purpose of Review

The treatment of advanced melanoma has changed dramatically in recent years with several new drugs having been approved for the treatment of melanoma since 2011. This review aims to evaluate the role of BRAF-targeted therapy for advanced melanoma in the immunotherapy era.

Recent Findings

Currently, in patients with BRAF wild-type advanced melanoma, anti-PD-1 (nivolumab or pembrolizumab) is the main treatment. The combination of nivolumab and ipilimumab (anti-CTLA-4) is also an important option for these patients, resulting in a better outcome, but with less favorable toxicity profile. In patients with BRAF mutations, three regimens of BRAF plus MEK inhibitors are now approved (vemurafenib plus cobimetinib, dabrafenib plus trametinib, and encorafenib plus binimetinib), which achieve rapid antitumor responses and a significant survival benefit. In these patients, as well as in BRAF wild-type patients, immunotherapy can be also effective and is regularly used.

Summary

Immunotherapy and targeted therapy have become the new standards of care, substantially improving survival rates. However, many questions still remain unanswered, such as what is the best first- and second-line treatment and the best treatment sequence. New combinations of drugs, targeted therapy combined with immunotherapy, and sequencing approaches are now underway in many ongoing clinical trials.

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Funding

This work was supported by grants from Italian Ministry of Health (IT-MOH) through “ Ricerca Corrente.”

AS and MP is funded by Istitutional “Ricerca Corrente.”

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Affiliations

  1. Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Via Mariano Semmola snc, Naples, Italy

    Vito Vanella, Lucia Festino, Claudia Trojaniello, Maria Grazia Vitale, Antonio Sorrentino, Miriam Paone & Paolo A. Ascierto

  2. Department of Medicine (DAME), University Hospital of Udine, Udine, Italy

    Maria Grazia Vitale

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  1. Vito Vanella
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  2. Lucia Festino
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Conflict of Interest

Vito Vanella has received compensation from MSD for service as a consultant.

Lucia Festino has received compensation from MSD for service as a consultant.

Claudia Trojaniello has received compensation from MSD for service as a consultant.

Maria Grazia Vitale declares that she has no conflict of interest.

Antonio Sorrentino declares that he has no conflict of interest.

Miriam Paone declares that she has no conflict of interest.

Paolo A. Ascierto has received research funding from Bristol-Myers Squibb, Roche-Genentech, and Array; has received travel support from MSD; and has received compensation from Bristol-Myers Squibb, Roche-Genentech, MSD, Array BioPharma, Amgen, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, NewLink Genetics, MedImmune, AstraZeneca, Syndax, Sun Pharmaceutical Industries Ltd., Sanofi, Idera, Ultimovacs, Sandoz, and Immunocore for service as a consultant.

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Vanella, V., Festino, L., Trojaniello, C. et al. The Role of BRAF-Targeted Therapy for Advanced Melanoma in the Immunotherapy Era. Curr Oncol Rep 21, 76 (2019). https://doi.org/10.1007/s11912-019-0827-x

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Keywords

  • Melanoma
  • Immunotherapy
  • Targeted therapy
  • CTLA-4
  • PD-1
  • Ipilimumab
  • Nivolumab
  • Pembrolizumab
  • Vemurafenib
  • Cobimetinib
  • Dabrafenib
  • Trametinib
  • Encorafenib
  • Binimetinib
  • Combination
  • Sequencing