背景:基于抗PD-1的免疫疗法被认为是晚期BRAFV600突变型黑色素瘤的首选一线治疗方法。然而,最近的一项国际多中心研究表明,在非肢端皮肤亚型的亚洲患者中,免疫治疗的疗效较差.我们假设亚洲患者的最佳一线治疗可能有所不同。
方法:我们回顾性收集了接受一线BRAF/MEK抑制剂(BRAF/MEKi)治疗的亚洲晚期BRAFV600突变黑色素瘤患者的数据,抗PD-1单一疗法(抗PD-1),2016年至2021年,来自日本28家机构的nivolumab联合ipilimumab(PD-1/CTLA-4)。
结果:我们确定了336例接受BRAF/MEKi治疗的患者(n=236),抗PD-1(n=64)和PD-1/CTLA-4(n=36)。所有患者的中位随访时间为19.9个月,184名在最后一次随访时存活的患者的中位随访时间为28.6个月。对于接受BRAF/MEKi治疗的患者,抗PD-1,PD-1/CTLA-4,基线时的中位年龄为62岁,62岁和53岁(p=0.03);客观缓解率为69%,27%,和28%(p<0.001);中位无进展生存期(PFS)为14.7、5.4和5.8个月(p=0.003),中位总生存期(OS)为34.6、37.0个月,没有达到,分别(p=0.535)。在多变量分析中,与BRAF/MEKi相比,抗PD-1和PD-1/CTLA-4PFS的风险比(HR)分别为2.30(p<0.001)和1.38(p=0.147),对于操作系统,HR分别为1.37(p=0.111)和0.56(p=0.075),分别。在倾向得分匹配中,BRAF/MEKi与PD-1/CTLA-4显示出更长的PFS和等效OS的趋势(PD-1/CTLA-4的HR为1.78[p=0.149])和1.03[p=0.953],分别)。对于接受二线治疗的患者,BRAF/MEKi和PD-1/CTLA-4显示较差的生存结果。
结论:在亚洲患者中,PD-1/CTLA-4优于BRAF/MEKi。一线BRAF/MEKi仍然可行,但是很难在进展中挽救。在选择系统疗法时,应考虑种族,直到个性化的生物标志物在日常实践中可用。需要进一步的研究来确定亚洲患者的最佳治疗顺序。
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.