Bylicki Olivier, Guisier Florian, Monnet Isabelle, Doubre Hélène, Gervais Radj, Janicot Henri, Perol Maurice, Fournel Pierre, Lamy Régine, Auliac Jean-Bernard, Chouaid Christos
Service de Pneumologie, Hôpital d'Instruction des Armées Percy, Clamart.
Service de Pneumologie, Centre Hospitalier Universitaire de Rouen, Rouen.
Medicine (Baltimore). 2020 Jan;99(3):e18726. doi: 10.1097/MD.0000000000018726.
Immune-checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC) harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting.In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK- or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation.Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61% were never-smokers and 59% were women. Among them, 82% had EGFR-activating mutations, 16% ALK translocations, or 2% ROS1 translocations. Before ICI therapy, patients had received a median of 3 treatment lines (including tyrosine-kinase inhibitor). The median PFS was 2.1 (95% confidence interval [CI], 1.5-3.2) months for the entire cohort, 2.2 (95% CI, 1.4-3.2) for EGFR-mutated patients, and 2.4 (95% CI, 2.1-not reached) months for ALK-translocated patients. The median OS was 14.7 (95% CI, 12.1-19.2) months for the entire population and 13.9 (95% CI, 8.8-20.0) and 19.2 (95% CI, 13.1-not reached) months for EGFR-mutated and ALK-translocated patients, respectively. Seven (13.7%) patients were treated with ICI for >9 months. Toxicities were reported in 22% (11/51), including 8% (4/51) grade ≥3.In this real-world setting, analysis of ICI PFS against EGFR-mutated or ALK-translocated NSCLC patients appeared close to that observed in pretreated unselected NSCLC patients. The more promising OS probably linked to post-ICI treatments. Large prospective studies on these patient subsets are needed.
免疫检查点抑制剂（ICI）在伴有分子改变的非小细胞肺癌（NSCLC）患者中的疗效仍未得到充分阐明。本研究旨在确定在真实世界中ICI对表皮生长因子受体（EGFR）/间变性淋巴瘤激酶（ALK）/原癌基因c-ros1（ROS1）突变的NSCLC患者的疗效。在这项针对接受ICI治疗的EGFR突变或ALK或ROS1重排的NSCLC成人患者的回顾性多中心研究中，我们分析了临床特征和结局：ICI治疗持续时间、无进展生存期（PFS）、客观缓解率、缓解持续时间以及从免疫治疗开始后的总生存期（OS）。来自20个法国中心的51例NSCLC患者（平均年龄58.0岁）被纳入研究：61%为从不吸烟者，59%为女性。其中，82%有EGFR激活突变，16%有ALK易位，或2%有ROS1易位。在ICI治疗前，患者接受的治疗线数中位数为3线（包括酪氨酸激酶抑制剂）。整个队列的中位PFS为2.1（95%置信区间[CI]，1.5 - 3.2）个月，EGFR突变患者为2.2（95%CI，1.4 - 3.2）个月，ALK易位患者为2.4（95%CI，2.1 - 未达到）个月。整个人群的中位OS为14.7（95%CI，12.1 - 19.2）个月，EGFR突变和ALK易位患者分别为13.9（95%CI，8.8 - 20.0）个月和19.2（95%CI，13.1 - 未达到）个月。7例（13.7%）患者接受ICI治疗超过9个月。22%（11/51）的患者报告了毒性反应，包括8%（4/51）≥3级毒性反应。在这个真实世界环境中，针对EGFR突变或ALK易位的NSCLC患者的ICI PFS分析似乎与在未经选择的预处理NSCLC患者中观察到的情况相近。更有前景的OS可能与ICI治疗后的治疗有关。需要对这些患者亚组进行大型前瞻性研究。
