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

Fiche publication

Date publication

juin 2020

Journal

Cancers

Auteurs

Membres identifiés du Cancéropôle Est :
Pr AUBIN François

Tous les auteurs :
Huynh S, Mortier L, Dutriaux C, Maubec E, Boileau M, Dereure O, Leccia MT, Arnault JP, Brunet-Possenti F, Aubin F, Dreno B, Beylot-Barry M, Lebbe C, Lefevre W, Delyon J

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32585901

Résumé

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.