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

Cancers

Caroline Dutriaux¹  Marie Beylot-Barry¹  Olivier Dereure²  Eve Maubec³  Florence Brunet-Possenti⁴  Sandra Huynh⁵  Wendy Lefevre⁵  Julie Delyon⁵  Celeste Lebbe⁵  Brigitte Dreno⁶  Jean-Philippe Arnault⁷  Marie-Therese Leccia⁸  Francois Aubin⁹  Marie Boileau^1,10  Laurent Mortier^1,11 

[1] Department of Dermatology, Bordeaux Universitary Hospital, 33000 Bordeaux, France;Department of Dermatology, University of Montpellier, 34090 Montpellier, France;Dermatology Department, AP-HP Hôpital Avicenne, Université Paris 13, 93000 Bobigny, France;Dermatology Department, AP-HP Hôpital Bichat, 75018 Paris, France;Dermatology Department, AP-HP Hôpital Saint-Louis, 75010 Paris, France;Dermatology Department, CHU de Nantes, 44000 Nantes, France;Dermatology Department, CHU d’Amiens-Picardie Site Nord, 80080 Amiens, France;Dermatology Department, Hôpital Albert Michallon, 38700 Grenoble, France;Dermatology Department, Hôpital Jean Minjoz, 25000 Besançon, France;Service de Dermatologie, Universite de Lille, CHU de Lille, 59000 Lille, France;Service de Dermatologie, Universite de Lille, Inserm U1189, CHU de Lille, 59000 Lille, France;

关键词: anti-PD1;    targeted therapy;    BRAF inhibitor;    MEK inhibitor;    melanoma;   

DOI  :  10.3390/cancers12061666

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown