Huang Letian, Zhang Shuling, Sun Li, Ma Jietao, Han Chengbo
Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
JCO Precis Oncol. 2025 Jul;9:e2400907. doi: 10.1200/PO-24-00907. Epub 2025 Jul 10.
The efficacy and safety of combination strategies involving immune checkpoint inhibitors (ICIs) in patients with advanced epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC) who have developed resistance to EGFR-tyrosine kinase inhibitors (TKIs) remains uncertain.
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ICIs combined with chemotherapy with or without antiangiogenic therapy (C/A) versus C/A alone in the treatment of advanced NSCLC after resistance to EGFR-TKIs. We searched databases, including PubMed, Cochrane Library, Embase, Web of Science, and meeting abstracts. Hazard ratios (HRs) and 95% CI for median overall survival (OS) and median progression-free survival (PFS) were calculated. Risk ratios (RRs) and 95% CI were used as indicators of objective response rate (ORR) and adverse events (AEs).
Eight RCTs involving 10 cohorts and 2,269 patients were included. Adding ICIs to C/A significantly improved PFS (HR, 0.67 [95% CI, 0.57 to 0.80]; < .001), OS (HR, 0.89 [95% CI, 0.79 to 0.99]; = .031), and ORR (RR, 0.80 [95% CI, 0.74 to 0.88]; < .001) comparedwith C/A alone. Subgroup analyses showed that the benefits were more pronounced in patients with PD-L1 expression ≥50%, specific mutations (Leu858Arg), absence of Thr790Met mutation, and treatment with pemetrexed-platinum. No significant increase in grade 3 or higher AEs was observed, but rates of discontinuation and specific AEs (rash, hypothyroidism, and hypertension) were significantly higher in the ICI+C/A group.
This meta-analysis suggests that the addition of ICIs to C/A may improve survival outcomes in patients with advanced NSCLC after resistance to EGFR-TKIs, particularly in selected subpopulations such as those with high PD-L1 expression or specific mutations. However, careful monitoring for specific AEs is warranted.
对于已对表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）产生耐药性的晚期EGFR突变型非小细胞肺癌（NSCLC）患者，涉及免疫检查点抑制剂（ICI）的联合治疗策略的疗效和安全性仍不确定。
我们对随机对照试验（RCT）进行了系统评价和荟萃分析，比较了ICI联合化疗（联合或不联合抗血管生成治疗，即C/A）与单纯C/A治疗EGFR-TKI耐药后的晚期NSCLC的疗效。我们检索了包括PubMed、Cochrane图书馆、Embase、科学网和会议摘要在内的数据库。计算了中位总生存期（OS）和中位无进展生存期（PFS）的风险比（HR）及95%置信区间（CI）。风险比（RR）及95%CI用作客观缓解率（ORR）和不良事件（AE）的指标。
纳入了8项RCT，涉及10个队列和2269例患者。与单纯C/A相比，在C/A基础上加用ICI可显著改善PFS（HR，0.67[95%CI，0.57至0.80]；P<0.001）、OS（HR，0.89[95%CI，0.79至0.99]；P=0.031）和ORR（RR，0.80[95%CI，0.74至0.88]；P<0.001）。亚组分析表明，在PD-L1表达≥50%、特定EGFR突变（Leu858Arg）、无Thr790Met突变以及接受培美曲塞-铂类治疗的患者中，获益更为显著。未观察到3级或更高等级AE的显著增加，但ICI+C/A组的停药率和特定AE（皮疹、甲状腺功能减退和高血压）发生率显著更高。
这项荟萃分析表明，在C/A基础上加用ICI可能改善EGFR-TKI耐药后的晚期NSCLC患者的生存结局，特别是在选定的亚组人群中，如PD-L1高表达或特定EGFR突变的患者。然而，需要对特定AE进行仔细监测。
