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Updates in Targeted Combination Therapies for Melanoma

Caroline Seymour
Published: Thursday, Feb 08, 2018

Paul B. Chapman, MD

Paul B. Chapman, MD
Approximately 40% of melanoma cases harbor BRAF mutations that are able to be targeted, and with the advent of the combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) demonstrating impressive outcomes in patients with BRAF mutations, physicians are no longer using BRAF inhibitors alone, but rather in combination with MEK inhibitors due to the improved efficacy.

Looking forward, Chapman said that targeted therapies may be used with deference to immunotherapy, but there are no long-term data directly comparing targeted therapy and immunotherapy. However, recent data on the long-term follow-up of patients on BRAF/MEK inhibitor combination therapy have led researchers to hypothesize that the potential of targeted therapies to facilitate steady OS may not be as distinct from immunotherapies as previously believed. Current research that is looking to combine the 2 therapies may abnegate the need to select a frontline therapy altogether, he concluded.


  1. Long GV, Stroyakovskiy D, Gogas H, Levchenko E. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371:1877-1888. doi: 10.1056/NEJMoa1406037.
  2. Long GV, Hauschild A, Santinami M, et al. Efficacy outcomes in the phase 3 COMBI-AD study of adjuvant dabrafenib (D) plus trametinib (T) vs placebo (PBO) in patients (pts) with stage III BRAF V600E/K–mutant melanoma. In: Proceedings of the 2017 World Congress of Melanoma; October 18-21, 2017; Brisbane, Australia. Presentation SMR09-1.
  3. Das Thakur M, Stuart DD. The evolution of melanoma resistance reveals therapeutic opportunities. Cancer Res. 2013;73(20):6106-6110. doi: 10.1158/0008-5472.CAN-13-1633.

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