Department of Pulmonary Medicine, Sendai Kousei Hospital, Aoba-ku, Sendai, Miyagi, Japan.
Oncologist. 2020 Mar;25(3):e536-e544. doi: 10.1634/theoncologist.2019-0550. Epub 2019 Nov 7.
Anti-programmed cell death 1 antibody is a standard therapy for advanced non-small cell lung cancer (NSCLC). However, immune-related adverse events (irAEs), such as skin reactions, are frequently observed. Although skin reactions are associated with clinical efficacy in melanoma, this association in advanced NSCLC and predictors of irAEs remain unclear. Accordingly, this study identified potential correlations of skin reactions with clinical efficacy and clinical predictors of development of skin reactions.
SUBJECTS, MATERIALS, AND METHODS: We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 155) during January 2016 to April 2018. Treatment efficacy was evaluated in patients with and without skin reactions, and associated predictive markers were determined. A 6-week landmark analysis was conducted to assess the clinical benefit of early skin reactions.
Skin reactions were observed in 51 patients with a median time to onset of 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions (57% vs. 19%, p < .001). Median progression-free survival (PFS) durations of 12.9 and 3.5 months and overall survival durations of not reached and 11.4 months were observed in patients with and without skin reactions, respectively. In the 6-week landmark analysis, the ORR was significantly higher in patients with skin reactions, and skin reactions were significantly associated with increased PFS. A multivariate analysis identified pre-existing rheumatoid factor (RF) as an independent predictor of skin reactions.
Skin reactions appeared beneficial in patients treated with nivolumab/pembrolizumab for advanced NSCLC and could be predicted by pre-existing RF. Further large-scale validations studies are warranted.
This single-institutional medical record review that included 155 patients with advanced non-small cell lung cancer who were treated with nivolumab or pembrolizumab monotherapy revealed that overall response rate and progression-free survival were significantly better in patients with skin reactions. Pre-existing rheumatoid factor was an independent predictor of skin reactions.
抗程序性死亡 1 抗体是晚期非小细胞肺癌（NSCLC）的标准治疗方法。然而，经常观察到免疫相关的不良反应（irAEs），如皮肤反应。尽管皮肤反应与黑色素瘤的临床疗效相关，但在晚期 NSCLC 中，这种相关性和 irAEs 的预测因素尚不清楚。因此，本研究确定了皮肤反应与临床疗效的潜在相关性，并确定了皮肤反应发展的临床预测因素。
受试者、材料和方法：我们回顾性调查了 2016 年 1 月至 2018 年 4 月在仙台 Kousei 医院接受nivolumab 或 pembrolizumab 单药治疗的晚期 NSCLC 患者（n=155）。评估了有和没有皮肤反应的患者的治疗效果，并确定了相关的预测标志物。进行了 6 周的里程碑分析，以评估早期皮肤反应的临床获益。
51 例患者出现皮肤反应，中位发病时间为 6.4 周。有皮肤反应的患者总体缓解率（ORR）显著更高（57% vs. 19%，p<0.001）。有和没有皮肤反应的患者中位无进展生存期（PFS）分别为 12.9 和 3.5 个月，总生存期分别为未达到和 11.4 个月。在 6 周的里程碑分析中，有皮肤反应的患者 ORR 显著更高，皮肤反应与 PFS 延长显著相关。多变量分析确定了预先存在的类风湿因子（RF）是皮肤反应的独立预测因素。
皮肤反应似乎对接受 nivolumab/pembrolizumab 治疗的晚期 NSCLC 患者有益，并且可以通过预先存在的 RF 来预测。需要进一步的大规模验证研究。
这项包括 155 例接受 nivolumab 或 pembrolizumab 单药治疗的晚期非小细胞肺癌患者的单机构病历回顾性研究表明，有皮肤反应的患者的总缓解率和无进展生存期显著更好。预先存在的类风湿因子是皮肤反应的独立预测因素。
