抗PD-1免疫疗法被认为是晚期BRAF V600突变型黑色素瘤首选的一线治疗方法。然而，最近一项国际多中心研究表明，免疫疗法在非乳头状皮肤亚型的亚洲患者中的疗效较差。我们假设亚洲患者的最佳一线治疗可能不同。我们回顾性收集了来自日本28个医疗机构2016年至2021年间接受一线BRAF/MEK抑制剂（BRAF/MEKi），抗PD-1单药疗法（抗PD-1）和尼伐莫布加伊匹美坦（PD-1/CTLA-4）治疗的亚洲BRAF V600突变型晚期黑色素瘤患者的数据。我们确定了336名接受BRAF/MEKi治疗的患者（n = 236），抗PD-1治疗的患者（n = 64）和PD-1/CTLA-4治疗的患者（n = 36）。对于所有患者，中位随访持续时间为19.9个月，对于184名在最后一次随访时仍活着的患者，中位随访持续时间为28.6个月。对于接受BRAF/MEKi、抗PD-1和PD-1/CTLA-4治疗的患者，基线时的中位年龄分别为62岁、62岁和53岁（p = 0.03）；客观缓解率分别为69％、27％和28％（p <0.001）；中位无进展生存期（PFS）分别为14.7个月、5.4个月和5.8个月（p = 0.003），中位总生存期（OS）分别为34.6个月、37.0个月和未达到（p = 0.535）。在多变量分析中，与BRAF/MEKi相比，抗PD-1和PD-1/CTLA-4的PFS风险比分别为2.30（p <0.001）和1.38（p = 0.147），OS风险比分别为1.37（p = 0.111）和0.56（p = 0.075）。在倾向评分匹配中，BRAF/MEKi显示出较长的PFS和与PD-1/CTLA-4相当的OS（PD-1/CTLA-4的HR分别为1.78 [p = 0.149]和1.03 [p = 0.953]）。对于接受二线治疗的患者，BRAF/MEKi后接PD-1/CTLA-4显示出较差的生存结果。PD-1/CTLA-4相较于BRAF/MEKi在亚洲患者中的优势似乎有限。一线BRAF/MEKi仍然可行，但在进展过程中难以拯救。在选择系统治疗时，应考虑种族因素，直到在日常实践中出现个性化的生物标志物。还需要进一步研究以确定亚洲患者的最佳治疗顺序。© 2023 The Authors. Cancer Medicine由John Wiley & Sons Ltd发表。

Anti-PD-1-based immunotherapy is considered a preferred first-line treatment for advanced BRAF V600-mutant melanoma. However, a recent international multi-center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non-acral cutaneous subtype. We hypothesized that the optimal first-line treatment for Asian patients may be different.We retrospectively collected data of Asian patients with advanced BRAF V600-mutant melanoma treated with first-line BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (Anti-PD-1), and nivolumab plus ipilimumab (PD-1/CTLA-4) between 2016 and 2021 from 28 institutions in Japan.We identified 336 patients treated with BRAF/MEKi (n = 236), Anti-PD-1 (n = 64) and PD-1/CTLA-4 (n = 36). The median follow-up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow-up. For patients treated with BRAF/MEKi, anti-PD-1, PD-1/CTLA-4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p < 0.001); median progression-free survival (PFS) was 14.7, 5.4, and 5.8 months (p = 0.003), and median overall survival (OS) was 34.6, 37.0 months, and not reached, respectively (p = 0.535). In multivariable analysis, hazard ratios (HRs) for PFS of Anti-PD-1 and PD-1/CTLA-4 compared with BRAF/MEKi were 2.30 (p < 0.001) and 1.38 (p = 0.147), and for OS, HRs were 1.37 (p = 0.111) and 0.56 (p = 0.075), respectively. In propensity-score matching, BRAF/MEKi showed a tendency for longer PFS and equivalent OS with PD-1/CTLA-4 (HRs for PD-1/CTLA-4 were 1.78 [p = 0.149]) and 1.03 [p = 0.953], respectively). For patients who received second-line treatment, BRAF/MEKi followed by PD-1/CTLA-4 showed poor survival outcomes.The superiority of PD-1/CTLA-4 over BRAF/MEKi appears modest in Asian patients. First-line BRAF/MEKi remains feasible, but it is difficult to salvage at progression. Ethnicity should be considered when selecting systemic therapies until personalized biomarkers are available in daily practice. Further studies are needed to establish the optimal treatment sequence for Asian patients.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.