Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.
Front Immunol. 2021 Jul 5;12:691032. doi: 10.3389/fimmu.2021.691032. eCollection 2021.
Anti-PD-1 monotherapy is the standard therapy for advanced melanoma patients, including those with NRAS mutations. The influence of NRAS mutation on immunotherapy, especially in noncutaneous melanoma, is largely uncharacterized.
We analyzed clinical data of four clinical trials for advanced melanoma patients treated with anti-PD-1 monotherapy between 2016 and 2019. The impact of NRAS mutation on efficacy and outcome of immunotherapy were analyzed in cutaneous and noncutaneous groups separately.
A total of 206 patients were assessed, including 92 cutaneous melanoma patients with 12 NRAS mutations and 114 noncutaneous melanoma patients with 21 NRAS mutations. In cutaneous melanoma, the response rates of NRAS mutant patients were lower than patients without NRAS mutations (9.5% . 23.9%), the median progression-free survival (PFS) and median overall survival (OS) were shorter for patients with NRAS mutations, although without significant difference for OS (P=0.081). In noncutaneous melanoma, the response rates were 0 and 13.7% for NRAS mutant and wild-type patients, the median PFS were 3.6 months (95% CI: 0.9-6.3) and 4.3 months (95%CI: 2.9-5.7) (P=0.015), and the median OS were 10.8 months (95% CI: 1.5-20.1) and 15.3 months (95% CI: 13.2-17.4) (P=0.025), respectively. In multivariate analysis, NRAS mutation, along with ECOG performance score and LDH level, was negatively associated with both PFS (HR 1.912, P=0.044) and OS (HR 2.210, P=0.025) in noncutaneous melanoma.
In advanced Asian melanoma treated with anti-PD-1 monotherapy, NRAS mutant patients had lower response rates and poorer prognoses compared to wild-type patients, especially in noncutaneous subtypes.
抗 PD-1 单药治疗是晚期黑色素瘤患者的标准治疗方法，包括NRAS 突变患者。NRAS 突变对免疫治疗的影响，尤其是在非皮肤黑色素瘤中，很大程度上尚未确定。
我们分析了 2016 年至 2019 年间接受抗 PD-1 单药治疗的晚期黑色素瘤患者的四项临床试验的临床数据。分别分析了皮肤和非皮肤组中 NRAS 突变对免疫治疗疗效和结局的影响。
共评估了 206 例患者，包括 92 例皮肤黑色素瘤患者（12 例 NRAS 突变）和 114 例非皮肤黑色素瘤患者（21 例 NRAS 突变）。在皮肤黑色素瘤中，NRAS 突变患者的反应率低于无 NRAS 突变患者（9.5% vs. 23.9%），NRAS 突变患者的中位无进展生存期（PFS）和中位总生存期（OS）较短，但 OS 无显著差异（P=0.081）。在非皮肤黑色素瘤中，NRAS 突变和野生型患者的反应率分别为 0%和 13.7%，中位 PFS 分别为 3.6 个月（95%CI：0.9-6.3）和 4.3 个月（95%CI：2.9-5.7）（P=0.015），中位 OS 分别为 10.8 个月（95%CI：1.5-20.1）和 15.3 个月（95%CI：13.2-17.4）（P=0.025）。多变量分析显示，NRAS 突变与 ECOG 表现评分和 LDH 水平与非皮肤黑色素瘤的 PFS（HR 1.912，P=0.044）和 OS（HR 2.210，P=0.025）均呈负相关。
在接受抗 PD-1 单药治疗的亚洲晚期黑色素瘤患者中，与野生型患者相比，NRAS 突变患者的反应率较低，预后较差，尤其是在非皮肤亚型中。
