University of Toronto Faculty of Medicine, Toronto, Ontario.
Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
Expert Rev Anticancer Ther. 2020 Feb;20(2):131-136. doi: 10.1080/14737140.2020.1724097. Epub 2020 Feb 5.
: Immune checkpoint inhibitor therapy and BRAF-targeted therapy have been developed for the treatment of metastatic melanoma. The optimal use of these agents, either in sequence or combination, for the 40-50% of melanoma patients whose tumors harbor a BRAFV600 mutation is unknown, but data from a number of clinical trials, including one randomized Phase II study, are emerging.: This review describes the preclinical and clinical rationale for combined BRAF-targeted therapy with immunotherapy, including the known effects of BRAF-targeted therapy on the immune microenvironment, and the clinical trial data from a number of studies.: BRAF-targeted therapy is associated with high response rates in patients with metastatic melanoma but also leads to changes in the tumor microenvironment that may sensitize these tumors to immunotherapy. The early trials of BRAF-targeted therapy with immunotherapy, in particular with anti-PD-1/PD-L1 agents, are encouraging and suggest that some patients may benefit from this treatment approach. However, incorporating these combinations into routine clinical practice requires the read-out from two randomized clinical trials expected in the coming 1-2 years.
: 免疫检查点抑制剂治疗和 BRAF 靶向治疗已被开发用于治疗转移性黑色素瘤。对于 40-50%的肿瘤携带 BRAFV600 突变的黑色素瘤患者，尚不清楚这些药物是序贯使用还是联合使用，但来自许多临床试验的数据，包括一项随机 II 期研究，正在出现。: 本综述描述了联合 BRAF 靶向治疗与免疫治疗的临床前和临床基础，包括 BRAF 靶向治疗对免疫微环境的已知影响，以及来自多项研究的临床试验数据。: BRAF 靶向治疗可使转移性黑色素瘤患者获得高应答率，但也会导致肿瘤微环境发生变化，从而使这些肿瘤对免疫治疗更敏感。BRAF 靶向治疗联合免疫治疗的早期试验，特别是与抗 PD-1/PD-L1 药物联合治疗，令人鼓舞，表明一些患者可能受益于这种治疗方法。然而，将这些组合纳入常规临床实践需要从未来 1-2 年内预计进行的两项随机临床试验中得出结论。
