Immunotherapy efficacy between exon 19 deletion and exon 21 L858R mutation in advanced EGFR mutant non-small-cell lung cancer: a direct and indirect meta-analysis.

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.