Li Xingyuan, Huang Huayan, Sun Yingjia, Jiang Qing, Yu Yongfeng
Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Respiratory and Critical Care Medicine, Fuyang People's Hospital, Fuyang, China.
Front Oncol. 2023 Oct 5;13:1265236. doi: 10.3389/fonc.2023.1265236. eCollection 2023.
This study aimed to investigate the efficacy of immunotherapy, as monotherapy or in combination, comparing to chemotherapy with or without anti-angiogenesis for advanced non-small cell lung cancer (NSCLC) patients progressing to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).
We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who received immune checkpoint inhibitors (ICI) and/or chemotherapy after EGFR-TKIs failure at Shanghai Chest Hospital between Aug 2016 and Oct 2022. According to the subsequent immunotherapy regimen, the patients were assigned to ICI monotherapy (IM), IO plus anti-angiogenesis (IA), ICI plus chemotherapy (IC), ICI plus chemotherapy plus anti-angiogenesis (ICA). Eligible patients undergoing standard chemotherapy were assigned to chemotherapy plus anti-angiogenesis (CA) and chemotherapy alone (CM). Efficacy was evaluated according to the RECIST 1.1version, and calculated the objective response rate (ORR) and disease control rate (DCR). Survival curves were plotted using the Kaplan-Meier method, and the median progression-free survival (PFS) was calculated. Differences among survival curves of the six groups were assessed using the log-rank test.
A total of 237 advanced NSCLC patients with EGFR mutations were included in this study. Of the 160 patients who received immunotherapy, 57 received ICI monotherapy, 27 received ICI plus anti-angiogenesis therapy, 43 received ICI plus chemotherapy, and 33 received ICI plus anti-angiogenesis plus chemotherapy. 77 patients received standard chemotherapy, of which 30 received chemotherapy plus anti-angiogenesis and 47 received chemotherapy alone. Patients in ICA group showed significant longer PFS than IM (7.2 vs 1.9 months, =0.011), IA (7.2 vs 4.8 months, =0.009) and CM group (7.2 vs 4.4 months, =0.005). There was no significant difference in PFS between the ICA and IC (7.2 vs 5.6 months, =0.104) or CA (7.2 vs 6.7 months, =0.959) group. Meanwhile, the ICA group showed the highest ORR and DCR (36.4% and 90.9%) compared to the other five groups. The IC group had a higher ORR than the IA and CA group (32.6% vs 7.4% vs 10.0%, respectively), but the DCR was comparable (79.1% vs 74.1% vs 76.7%, respectively). The ORR of the CM group was 6.4% and the DCR was 66.0%. IM group showed the lowest ORR and DCR (1.8% and 36.8%). Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 9 (27.3%) patients in the ICA group, 6 (20.0%) in the CA group, 7 (14.9%) in the CM group, 5 (11.6%) in the IC group, 5 (8.8%) in the IM group, and 2 (7.4%) in the IA group.
NSCLC patients with positive EGFR mutations after EGFR-TKIs failure received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in ORR, DCR and mPFS.
本研究旨在调查免疫疗法作为单一疗法或联合疗法，与联合或不联合抗血管生成的化疗相比，对进展至表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs）的晚期非小细胞肺癌（NSCLC）患者的疗效。
我们回顾性分析了2016年8月至2022年10月期间在上海胸科医院接受EGFR-TKIs治疗失败后接受免疫检查点抑制剂（ICI）和/或化疗的EGFR突变的晚期NSCLC患者。根据后续免疫治疗方案，将患者分为ICI单一疗法（IM）、免疫治疗联合抗血管生成（IA）、ICI联合化疗（IC）、ICI联合化疗联合抗血管生成（ICA）。接受标准化疗的符合条件患者分为化疗联合抗血管生成（CA）和单纯化疗（CM）。根据RECIST 1.1版评估疗效，计算客观缓解率（ORR）和疾病控制率（DCR）。使用Kaplan-Meier方法绘制生存曲线，并计算中位无进展生存期（PFS）。使用对数秩检验评估六组生存曲线之间的差异。
本研究共纳入237例EGFR突变的晚期NSCLC患者。在接受免疫治疗的160例患者中，57例接受ICI单一疗法，27例接受ICI联合抗血管生成治疗，43例接受ICI联合化疗，33例接受ICI联合抗血管生成联合化疗。77例患者接受标准化疗，其中30例接受化疗联合抗血管生成，47例接受单纯化疗。ICA组患者的PFS显著长于IM组（7.2个月对1.9个月，P=0.011）、IA组（7.2个月对4.8个月,P=0.009）和CM组（7.2个月对4.4个月，P=0.005）。ICA组与IC组（7.2个月对5.6个月，P=0.104）或CA组（7.2个月对6.7个月，P=0.959）之间的PFS无显著差异。同时，与其他五组相比，ICA组的ORR和DCR最高（分别为36.4%和90.9%）。IC组的ORR高于IA组和CA组（分别为32.6%对7.4%对10.0%），但DCR相当（分别为79.1%对74.1%对76.7%）。CM组ORR为6.4%，DCR为66.0%。IM组ORR和DCR最低（分别为1.8%和36.8%）。ICA组9例（27.3%）患者发生3级或更严重的治疗相关不良事件（TRAEs），CA组6例（20.0%），CM组7例（14.9%）,IC组5例（11.6%），IM组5例（8.8%），IA组2例（7.4%）。
EGFR-TKIs治疗失败后EGFR突变阳性的NSCLC患者接受后续免疫治疗联合抗血管生成和化疗可能在ORR、DCR和mPFS方面有更多益处。
