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

Dermatology Department, AP-HP Hôpital Saint-Louis, 75010 Paris, France
Service de Dermatologie, Universite de Lille, Inserm U1189, CHU de Lille, 59000 Lille, France
Department of Dermatology, Bordeaux Universitary Hospital, 33000 Bordeaux, France
Dermatology Department, AP-HP Hôpital Avicenne, Université Paris 13, 93000 Bobigny, France
Service de Dermatologie, Universite de Lille, CHU de Lille, 59000 Lille, France
Department of Dermatology, University of Montpellier, 34090 Montpellier, France
Dermatology Department, Hôpital Albert Michallon, 38700 Grenoble, France
Dermatology Department, CHU d’Amiens-Picardie Site Nord, 80080 Amiens, France
Dermatology Department, AP-HP Hôpital Bichat, 75018 Paris, France
Dermatology Department, Hôpital Jean Minjoz, 25000 Besançon, France
Dermatology Department, CHU de Nantes, 44000 Nantes, France
INSERM U976, Team 1, Human Immunology Pathophysiology & Immunotherapy (HIPI), Université de Paris, F-75010 Paris, France
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1666;
Received: 29 May 2020 / Revised: 19 June 2020 / Accepted: 19 June 2020 / Published: 23 June 2020
(This article belongs to the Special Issue Targeted Therapies for Melanoma)
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. View Full-Text
Keywords: anti-PD1; targeted therapy; BRAF inhibitor; MEK inhibitor; melanoma anti-PD1; targeted therapy; BRAF inhibitor; MEK inhibitor; melanoma
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Huynh, S.; Mortier, L.; Dutriaux, C.; Maubec, E.; Boileau, M.; Dereure, O.; Leccia, M.-T.; Arnault, J.-P.; Brunet-Possenti, F.; Aubin, F.; Dreno, B.; Beylot-Barry, M.; Lebbe, C.; Lefevre, W.; Delyon, J. Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study. Cancers 2020, 12, 1666.

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