Chen Zihong, Pang Lanlan, Yang Yuwen, He Xinyi, Zhan Jianhua, Zhang Lin, Xiong Kangqiao, Fang Wenfeng, Zhang Li, Zhang Yaxiong
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Transl Lung Cancer Res. 2025 Feb 28;14(2):422-430. doi: 10.21037/tlcr-24-884. Epub 2025 Feb 12.
Immunotherapy (IO) exhibits poor therapeutic effect in epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). However, previous studies reveal different IO efficacy between exon 19 deletion (19 Del) and exon 21 L858R mutation (21 L858R). In this study, we aimed to evaluate the difference in IO efficacy between patients with EGFR 19 Del and EGFR 21 L858R.
IO data of response rate, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) stratified by EGFR subtypes were extracted and synthesized on random-effect model using odds ratios (ORs) for dichotomous data and hazard ratios (HRs) for survival data with 95% confidence interval (CI). Efficacy comparisons between 19 Del and 21 L858R were estimated through direct and indirect methods respectively.
A total of 15 studies that involved 1,209 EGFR-mutant advanced NSCLC patients with IO treatment were included (19 Del, n=676; 21 L858R, n=533). Based on the data from 11 studies for direct meta-analysis, patients with 19 Del had shorter PFS (HR =1.55; 95% CI: 1.21-1.98; P=0.001) and OS (HR =1.36; 95% CI: 1.04-1.78; P=0.02) and poorer DCR (OR =0.51; 95% CI: 0.29-0.87; P=0.02) than those with 21 L858R significantly. Indirect meta-analysis from four trials showed the same result that patients with 19 Del had significantly shorter PFS (HR =1.50; 95% CI: 1.09-2.07; P=0.01) than those with 21 L858R. Subgroup analyses also showed similar tendency that 21 L858R had more clinical benefit compared to 19 Del no matter whether IO monotherapy or IO combination.
For advanced EGFR mutant NSCLC patients, 21 L858R had superior IO efficacy compared with 19 Del.
免疫疗法（IO）在表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）中治疗效果不佳。然而，先前的研究揭示了外显子19缺失（19 Del）和外显子21 L858R突变（21 L858R）之间不同的IO疗效。在本研究中，我们旨在评估EGFR 19 Del患者和EGFR 21 L858R患者之间IO疗效的差异。
提取按EGFR亚型分层的IO的缓解率、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）数据，并使用二分类数据的优势比（OR）和生存数据的风险比（HR）以及95%置信区间（CI），在随机效应模型上进行综合分析。分别通过直接和间接方法估计19 Del和21 L858R之间的疗效差异。
共纳入15项涉及1209例接受IO治疗的EGFR突变晚期NSCLC患者的研究（19 Del，n = 676；21 L858R，n = 533）。基于11项研究的数据进行直接荟萃分析，19 Del患者的PFS（HR = 1.55；95% CI：1.21 - 1.98；P = 0.001）和OS（HR = 1.36；95% CI：1.04 - 1.78；P = 0.02）较短，DCR（OR = 0.51；95% CI：0.29 - 0.87；P = 0.02）显著低于21 L858R患者。四项试验的间接荟萃分析显示了相同的结果，即19 Del患者的PFS（HR = 1.50；95% CI：1.09 - 2.07；P = 0.01）显著短于21 L858R患者。亚组分析也显示了类似的趋势，无论IO单药治疗还是IO联合治疗，21 L858R相比19 Del都具有更多的临床获益。
对于晚期EGFR突变的NSCLC患者，21 L858R的IO疗效优于19 Del。
