Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations
Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations
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DOI：
10.1371/journal.pone.0215292
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发表时间：
2019-04-12
期刊：
影响因子：
3.7
通讯作者：
Kikuchi, Toshiaki
中科院分区：
文献类型：
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作者：
Sato, Miyuki;Watanabe, Satoshi;Kikuchi, Toshiaki
尽管程序性细胞死亡 1 (PD-1)/PD-配体 (L) 1 的阻断已证明对非小细胞肺癌 (NSCLC) 有希望且持久的临床反应，但具有表皮生长因子受体 (EGFR) 突变的 NSCLC 患者对 PD-1/PD-L1 抑制剂反应较差。之前的研究已经确定了一些预测性生物标志物，包括肿瘤细胞上 PD-L1 的表达，用于 NSCLC 患者的 PD-1/PD-L1 阻断疗法；然而，这些生物标志物在 EGFR 突变的 NSCLC 中的作用尚未阐明。本研究旨在评估 EGFR 突变 NSCLC 中 PD-1/PD-L1 抑制剂的预测生物标志物。我们回顾性分析了 9 名接受纳武单抗治疗的 EGFR 突变 NSCLC 患者。除一名患者外，所有患者在纳武单抗治疗前均接受了 EGFR 酪氨酸激酶抑制剂治疗。总体缓解率和中位无进展生存期分别为 11% 和 33 天（95% 置信区间 (CI)；7 至 51）。单变量分析显示，患者具有良好的体能状态（P = 0.11；风险比（HR）0.183，95% CI 0.0217至1.549）、高密度CD4（+）T细胞（P = 0.136；HR 0.313，95% CI 0.045至1.417）和高密度Foxp3（+）细胞（P = 0.09；HR 0.264，95% CI 0.0372 至 1.222）在肿瘤微环境中，纳武单抗往往具有更长的无进展生存期。多变量分析显示高密度的 CD4(+) T 细胞 (P = 0.005; HR
Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4(+) T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3(+) cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4(+) T cells (P = 0.005; HR