在酪氨酸激酶抑制剂 (TKI) 耐药、表皮生长因子受体 (EGFR) 突变的非小细胞肺癌 (NSCLC) 化疗中添加免疫检查点抑制剂的作用仍不清楚。我们进行了一项荟萃分析，以全面评估化学免疫治疗组合（有或没有血管内皮生长因子 (VEGF) 抑制）在 TKI 耐药、EGFR 突变 NSCLC 中的作用。我们系统地检索了 PubMed/MEDLINE 和关键年度会议论文集2018 年至 2024 年期间举行的会议，以确定评估化学免疫疗法组合并纳入 EGFR 突变 NSCLC 患者的随机研究。荟萃分析中纳入了六项随机 III 期试验（CheckMate-722、KEYNOTE-789、ORIENT-31、IMpower150、IMpower151 和 ATTLAS）。为了比较无进展生存期 (PFS) 和总生存期 (OS) 结果，我们从每项研究中提取了 EGFR 突变亚组的 PFS 和 OS 的风险比 (HR) 和 95% 置信区间 (CI)。我们使用具有逆方差加权的固定效应模型来估计化学免疫疗法组合（使用和不使用 VEGF 抑制剂）与对照组相比的 PFS 和 OS 的总体效应大小。总共纳入了 1772 名 EGFR 突变 NSCLC 患者。在化疗中添加程序性死亡配体 1 [PD-(L)1] 抑制剂可显着改善 PFS（HR 0.77，95% CI 0.67-0.88，P = 0.0002）。当同时使用 PD-(L)1 和 VEGF 抑制时，这种效果更大（PFS：HR 0.62，95% CI 0.52-0.73，P < 0.0001）。 PD-(L)1 联合化疗组的汇总 OS HR 为 0.86（95% CI 0.75-1.00，P = 0.0429），PD-(L)1 双化疗组的汇总 OS HR 为 0.98（95% CI 0.79-1.22，P = 0.8463） /VEGF 抑制。尽管 PFS 略有改善，尤其是在化疗中添加 PD-(L)1 和 VEGF 抑制剂时最为明显，但这两种策略都没有带来具有临床意义的 OS 改善。我们的结果不支持在 TKI 耐药、EGFR 突变肺癌中广泛使用化学免疫疗法。癌基因驱动的 NSCLC 迫切需要新的免疫治疗方法。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

The role of adding immune checkpoint inhibitors to chemotherapy in tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) remains unknown. We carried out a meta-analysis to comprehensively assess the role of chemoimmunotherapy combinations, with and without vascular endothelial growth factor (VEGF) inhibition, in TKI-resistant, EGFR-mutant NSCLC.We systemically searched PubMed/MEDLINE and the proceedings of key annual meetings between 2018 and 2024 to identify randomized studies that evaluated chemoimmunotherapy combinations and included patients with EGFR-mutant NSCLC. Six randomized, phase III trials (CheckMate-722, KEYNOTE-789, ORIENT-31, IMpower150, IMpower151, and ATTLAS) were included in the meta-analysis. To compare progression-free survival (PFS) and overall survival (OS) outcomes, we extracted hazard ratio (HR) and 95% confidence interval (CI) for PFS and OS for EGFR-mutant subgroups from each study. We used the fixed effects model with inverse variance weighting to estimate the overall effect sizes for PFS and OS for chemoimmunotherapy combinations (with and without VEGF inhibitors) versus control arms.A total of 1772 patients with EGFR-mutant NSCLC were included. Adding programmed death-ligand 1 [PD-(L)1] inhibitors to chemotherapy significantly improved PFS (HR 0.77, 95% CI 0.67-0.88, P = 0.0002). This effect was greater when both PD-(L)1 and VEGF inhibition were utilized (PFS: HR 0.62, 95% CI 0.52-0.73, P < 0.0001). The pooled OS HR was 0.86 (95% CI 0.75-1.00, P = 0.0429) with the chemotherapy + PD-(L)1 combinations and 0.98 (95% CI 0.79-1.22, P = 0.8463) with dual PD-(L)1/VEGF inhibition.Despite modest improvements in PFS, most pronounced when both PD-(L)1 and VEGF inhibitors are added to chemotherapy, neither strategy led to clinically meaningful improvements in OS. Our results do not support the broad use of chemoimmunotherapy combinations in TKI-resistant, EGFR-mutant lung cancer. Novel immunotherapy approaches are urgently needed for oncogene-driven NSCLC.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.