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Review
. 2020 Aug;21(4):493-504.
doi: 10.1007/s40257-020-00509-z.

Long-Term Outcomes in BRAF-Mutated Melanoma Treated with Combined Targeted Therapy or Immune Checkpoint Blockade: Are We Approaching a True Cure?

Patrick Schummer  1 , Bastian Schilling  2 , Anja Gesierich  1
Affiliations
Review

Long-Term Outcomes in BRAF-Mutated Melanoma Treated with Combined Targeted Therapy or Immune Checkpoint Blockade: Are We Approaching a True Cure?

Patrick Schummer et al. Am J Clin Dermatol. 2020 Aug.

Abstract

Approximately 50% of all melanomas harbor an activating BRAF mutation. In patients suffering from an advanced melanoma with such a somatic alteration, combined targeted therapy with a BRAF and MEK inhibitor can be applied to significantly increase the survival probability. Nevertheless, resistance mechanisms, as well as negative predictive biomarkers (elevated lactate dehydrogenase levels, high number of metastatic organ disease sites, brain metastasis), remain a major problem in treating melanoma patients. Recently, a landmark overall survival (OS) rate of 34% after 5 years of combined targeted therapy in treatment-naïve patients was reported. On the other hand, patients harboring a BRAF mutation and receiving first-line immune checkpoint blockade with ipilimumab plus nivolumab showed a 5-year OS rate of 60%. As indicated by these data, long-term survival can be reached in melanoma patients but it remains unclear if this is equivalent to reaching a true cure for metastatic melanoma. In this review, we summarize the recent results for combined targeted therapy and immunotherapy in advanced melanoma harboring an activating BRAF mutation and discuss the impact of baseline characteristics on long-term outcome.

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Conflict of interest statement

Patrick Schummer has received honoraria from Bristol-Myers Squibb (BMS), an institutional research grant from Novartis, and reports travel support from Novartis, Lilly and BMS outside the submitted work. Bastian Schilling reports grants and personal fees from BMS, MSD Sharp & Dohme and Pierre Fabre Pharmaceuticals, and personal fees from Incyte, Novartis, Roche, Pfizer and AMGEN outside the submitted work. Anja Gesierich reports advisory roles for BMS, MSD Sharp & Dohme, Novartis, Roche, Pierre Fabre Pharmaceuticals, Pfizer and Sanofi Genzyme, has received honoraria from MSD Sharp & Dohme, BMS and Roche, and travel support from BMS, MSD Sharp & Dohme, Novartis, Roche and Pierre Fabre Pharmaceuticals outside of the submitted work.

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