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. 2020 Jun 23;12(6):1666.
doi: 10.3390/cancers12061666.

Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study

Sandra Huynh  1 , Laurent Mortier  2 , Caroline Dutriaux  3 , Eve Maubec  4 , Marie Boileau  5 , Olivier Dereure  6 , Marie-Therese Leccia  7 , Jean-Philippe Arnault  8 , Florence Brunet-Possenti  9 , Francois Aubin  10 , Brigitte Dreno  11 , Marie Beylot-Barry  3 , Celeste Lebbe  1   12 , Wendy Lefevre  1 , Julie Delyon  1   12
Affiliations

Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study

Sandra Huynh et al. Cancers (Basel). .

Abstract

Despite significant progress in melanoma survival, therapeutic options are still needed in case of progression under immune checkpoint inhibitors (ICI), and resistance to targeted therapies (TT) in BRAF-mutated melanomas. This study aimed to assess the safety of combined ICI and TT as a rescue line in real-life clinical practice. We conducted a study within the prospective French multicentric MelBase cohort, including patients treated with a combination of anti-PD1 (pembrolizumab/nivolumab) and BRAF inhibitor (BRAFi: dabrafenib/vemurafenib) and/or MEK inhibitors (MEKi: trametinib/cobimetinib) for BRAF mutated or wild-type advanced melanoma. Fifty-nine patients were included: 30% received the triple combination, 34% an anti-PD1 and BRAFi, and 36% an anti-PD1 and MEKi. Grade 3-4 adverse events occurred in 12% of patients. Permanent discontinuation or dose reduction of one of the treatments for toxicity was reported in 14% and 7% of patients, respectively. In the BRAF wild-type subgroup, treatment with MEKi and anti-PD1 induced a tumor control rate of 83% and median progression-free survival of 7.1 months. The combination of anti-PD1 and BRAFi and/or MEKi was a safe rescue line for advanced melanoma patients previously treated with ICI/TT. The benefit of these combinations, specifically anti-PD1 and MEKi in BRAF wild-type melanoma patients, needs to be prospectively studied.

Keywords: BRAF inhibitor; MEK inhibitor; anti-PD1; melanoma; targeted therapy.

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Conflict of interest statement

C.L.: reports grants and personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche, personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, personal fees from Merck Serono, personal fees from Sanofi, outside the submitted work. J.D.: reports travel accommodations from Pierre Fabre and Roche, outside the submitted work. L.M.: reports personal fees from Bristol-Myers Squibb, personal fees from Roche, personal fees from MSD, personal fees from Novartis, personal fees from Merck, outside the submitted work. J.P.A.: reports personal fees from Bristol-Myers-Squibb, grants from BMS—Novartis—MSD, during the conduct of the study. B.D., C.D., E.M., F.A., F.B.P., M.B., M.B.B., M.T.L., O.D., S.H., W.L.: declare no conflict of interest.

Figures

Figure 1
Figure 1
Survival in the BRAF-mutant subgroup. (a) Progression-free survival in the BRAF-mutant subgroup. PFS: progression-free survival. (b) Overall survival in the BRAF-mutant subgroup. OS: overall survival; NR: not reached.
Figure 2
Figure 2
Progression-free survival in the BRAF-wild type subgroup. PFS: progression-free survival; NR: not reached.
See this image and copyright information in PMC

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