Zhou Chunyang, Wang Zijian, Fu Chengrui, Tao Hengmin, Liu Chengxin
Department of Radiation Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Ann Transl Med. 2023 Feb 15;11(3):157. doi: 10.21037/atm-22-6272. Epub 2023 Feb 10.
Acquired drug resistance to various tyrosine kinase inhibitor (TKI) inevitably develops in almost all epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). The present study aimed to evaluate the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for such patients after TKI failure and further explore the subpopulation that exhibited the most benefit.
A total of 102 EGFR-mutant NSCLC patients who received PD-1 inhibitors after developing resistance to EGFR-TKIs were included in the study. The primary endpoints were progression-free survival (PFS) and grade 3-5 adverse events (AEs), while the secondary endpoints were overall survival (OS), disease control rate (DCR) and subgroup analyses.
All the 102 patients received 2 or more lines of immunotherapy. The overall median PFS was 4.95 months [95% confidence interval (CI): 3.91-5.89 months]. The EGFR group showed a significant PFS benefit compared with the EGFR group (6.4 3.5 months, P=0.002), and likewise for the DCR between the 2 groups (EGFR EGFR group: 84.3% 66.7%, P=0.049). In addition, median PFS in the EGFR-negative group (6.47 months) was significantly longer than the EGFR-positive group (3.20 months) (P=0.003). The overall OS was 10.70 months (95% CI: 8.92-12.48 months), without a prognostic factor. There was a trend towards improved PFS and OS with combination therapy. The incidence of grade 3-5 treatment-related AEs was 19.6%, while the incidence of grade 3-5 immune-related AEs (irAEs) was 6.9%. Treatment-related AEs were similar in different mutation subtypes. The incidence of grade 3-5 irAEs was higher in the EGFR group (10.3%) compared with the EGFR group (5.9%), and likewise in the EGFR-negative group (10%) compared with the EGFR-positive group (2.6%).
After EGFR-TKI failure, PD-1 inhibitors provided better survival in advanced NSCLC for the EGFR subgroup and EGFR-negative subgroup, and there was a trend towards improved outcomes with combination therapy. In addition, toxicity was well tolerated. Our real-world study increased the population size and obtained a similar survival outcome compared from clinical trials.
几乎所有表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者都会不可避免地对各种酪氨酸激酶抑制剂（TKI）产生获得性耐药。本研究旨在评估程序性细胞死亡蛋白1（PD-1）抑制剂在TKI治疗失败后的此类患者中的疗效和安全性，并进一步探索获益最大的亚组人群。
本研究共纳入102例对EGFR-TKI产生耐药后接受PD-1抑制剂治疗的EGFR突变NSCLC患者。主要终点为无进展生存期（PFS）和3-5级不良事件（AE），次要终点为总生存期（OS）、疾病控制率（DCR）和亚组分析。
所有102例患者均接受了2线或更多线的免疫治疗。总体中位PFS为4.95个月[95%置信区间（CI）：3.91-5.89个月]。EGFR⁻组与EGFR⁺组相比，PFS有显著获益（6.4对3.5个月，P=0.002），两组间DCR情况同样如此（EGFR⁻组对EGFR⁺组：84.3%对66.7%，P=0.049）。此外，EGFR阴性组的中位PFS（6.47个月）显著长于EGFR阳性组（3.20个月）（P=0.003）。总体OS为10.70个月（95%CI：8.92-12.48个月），无预后因素。联合治疗有改善PFS和OS的趋势。3-5级治疗相关AE的发生率为19.6%，而3-5级免疫相关AE（irAE）的发生率为6.9%。不同突变亚型的治疗相关AE相似。EGFR⁻组3-5级irAE的发生率（10.3%）高于EGFR⁺组（5.9%），EGFR阴性组（10%）高于EGFR阳性组（2.6%）同样如此。
EGFR-TKI治疗失败后，PD-1抑制剂在晚期NSCLC的EGFR⁻亚组和EGFR阴性亚组中提供了更好的生存获益，联合治疗有改善结局的趋势。此外，毒性耐受性良好。我们的真实世界研究增加了样本量，并获得了与临床试验相似的生存结果。
