Nearly half of all metastatic melanoma patients possess the BRAF V600 mutation. Several therapies are approved for advanced stage melanoma, but it is unclear if there is a differential outcome to various immunotherapy regimens based on BRAF mutation status. We retrospectively analyzed a cohort of metastatic or unresectable melanoma patients who were treated with combination ipilimumab/nivolumab (ipi/nivo) or anti‐PD‐1 monotherapy, nivolumab, or pembrolizumab, as first‐line treatment. 235 previously untreated patients were identified in our study. Our univariate analysis showed no statistical difference in progression‐free survival (PFS) or overall survival (OS) with ipi/nivo versus anti‐PD‐1 monotherapy in the BRAF V600 mutant cohort, but there was improved PFS [HR: 0.48, 95% CI, 0.28–0.80] and OS [HR: 0.50, 95% CI, 0.26–0.96] with ipi/nivo compared to anti‐PD‐1 monotherapy in the BRAF WT group. After adjusting for known prognostic variables in our multivariable analysis, the BRAF WT cohort continued to show PFS and OS benefit with ipi/nivo compared to anti‐PD‐1 monotherapy. Our single‐institution analysis suggests ipi/nivo should be considered over anti‐PD‐1 monotherapy as the initial immunotherapy regimen for metastatic melanoma patients regardless of BRAF mutation status, but possibly with greater benefit in BRAF WT.

中文翻译：

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BRAF 突变状态对抗 PD-1 单药治疗与 ipilimumab/nivolumab 联合治疗初治晚期黑色素瘤临床结果的影响

近一半的转移性黑色素瘤患者具有 BRAF V600 突变。几种疗法被批准用于晚期黑色素瘤，但尚不清楚基于 BRAF 突变状态的各种免疫疗法是否存在不同的结果。我们回顾性分析了一组转移性或不可切除的黑色素瘤患者，这些患者接受了 ipilimumab/nivolumab (ipi/nivo) 或抗 PD-1 单药治疗、nivolumab 或 pembrolizumab 作为一线治疗。在我们的研究中确定了 235 名以前未经治疗的患者。我们的单变量分析显示，在 BRAF V600 突变队列中，ipi/nivo 与抗 PD-1 单药治疗的无进展生存期 (PFS) 或总生存期 (OS) 没有统计学差异，但 PFS 有所改善 [HR: 0.48, 95 % CI, 0.28–0.80] 和 OS [HR: 0.50, 95% CI, 0.26–0。[96] 与 BRAF WT 组中的抗 PD-1 单药治疗相比，使用 ipi/nivo。在我们的多变量分析中调整了已知的预后变量后，与抗 PD-1 单药治疗相比，BRAF WT 队列继续显示 ipi/nivo 对 PFS 和 OS 的益处。我们的单机构分析表明，无论 BRAF 突变状态如何，都应考虑将 ipi/nivo 而非抗 PD-1 单一疗法作为转移性黑色素瘤患者的初始免疫治疗方案，但可能对 BRAF WT 有更大的益处。