Huynh Sandra, Mortier Laurent, Dutriaux Caroline, Maubec Eve, Boileau Marie, Dereure Olivier, Leccia Marie-Therese, Arnault Jean-Philippe, Brunet-Possenti Florence, Aubin Francois, Dreno Brigitte, Beylot-Barry Marie, Lebbe Celeste, Lefevre Wendy, Delyon Julie
Dermatology Department, AP-HP Hôpital Saint-Louis, 75010 Paris, France.
Service de Dermatologie, Universite de Lille, Inserm U1189, CHU de Lille, 59000 Lille, France.
Cancers (Basel). 2020 Jun 23;12(6):1666. doi: 10.3390/cancers12061666.
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.
尽管黑色素瘤生存率取得了显著进展，但在免疫检查点抑制剂（ICI）治疗期间病情进展以及BRAF突变型黑色素瘤对靶向治疗（TT）耐药的情况下，仍需要更多治疗选择。本研究旨在评估在现实临床实践中联合使用ICI和TT作为挽救治疗方案的安全性。我们在法国前瞻性多中心MelBase队列中开展了一项研究，纳入了接受抗PD1（帕博利珠单抗/纳武利尤单抗）与BRAF抑制剂（BRAFi：达拉非尼/维莫非尼）和/或MEK抑制剂（MEKi：曲美替尼/考比替尼）联合治疗的BRAF突变型或野生型晚期黑色素瘤患者。共纳入59例患者：30%接受三联疗法，34%接受抗PD1与BRAFi联合治疗，36%接受抗PD1与MEKi联合治疗。12%的患者发生3-4级不良事件。分别有14%和7%的患者因毒性反应导致其中一种治疗永久停药或减量。在BRAF野生型亚组中，MEKi与抗PD1联合治疗的疾病控制率为83%，中位无进展生存期为7.1个月。对于先前接受过ICI/TT治疗的晚期黑色素瘤患者，抗PD1与BRAFi和/或MEKi联合治疗是一种安全的挽救治疗方案。这些联合治疗方案，特别是BRAF野生型黑色素瘤患者中抗PD1与MEKi联合治疗的益处，需要进行前瞻性研究。
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