Metastatic melanoma: which BRAF/MEK inhibitor combination is best?

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  • Indirect comparison of dabrafenib (Tafinlar) plus trametinib (Mekinist) with vemurafenib (Zelboraf) plus cobimetinib (Cotellic) suggests the 2 combinations have similar efficacy in metastatic melanoma, but adverse events are lower with dabrafenib plus trametinib.
Why this matters
  • These findings can help providers in the decision-making process when they are evaluating available options of BRAF/MEK inhibitor combinations for this population.
Study design
  • As there are no head-to-head studies, an indirect comparison was performed between dabrafenib plus trametinib and vemurafenib plus cobimetinib; 2 randomized trials were identified (dabrafenib plus trametinib vs vemurafenib with 704 patients and vemurafenib plus cobimetinib vs vemurafenib plus placebo with 495 patients).
  • Funding: Novartis.
Key results
  • The HR for OS and PFS and the overall response rate (ORR) for the 2 combinations was statistically nonsignificant.
  • For OS and PFS, the HR was 0.94 (P=.7227) and 1.05 (P=.730), respectively, and the ORR had a risk ratio (RR) of 0.90 (P=.3029).
  • Subgroup analyses showed no significant differences between the 2 combination therapies.
  • The incidence of any adverse event (RR, 0.92; P=.0015), any grade ≥3 adverse event (RR, 0.71; P=.0002), dose interruption/modification (RR, 0.77; P=.0471) were all significantly reduced with dabrafenib plus trametinib.
  • Not a head-to-head trial.