Because patients with EGFR mutations are often excluded from big immunotherapy-based NSCLC trials, the activity of immune checkpoint inhibitors (ICIs) in NSCLC carrying EGFR exon 20 insertion mutations (ex20ins) has yet to be closely explored. Therefore, the results of ICI treatment for patients with EGFR ex20ins and wildtype NSCLC were compared in a retrospective, real-world investigation (wt-NSCLC; defined as EGFR and ALK test negative). Patients with advanced NSCLC were included in the analysis from the Flatiron Health Database (2015-2020). The primary and secondary objectives of this study were rwTTNT (real-world time to next therapy) and rwOS (overall real-world survival), respectively, both stratified by ICI’s beginning line of therapy.

About 25% of patients with EGFR ex20ins NSCLC and 39% of patients with wt-NSCLC were treated with ICI as first-line therapy. The adjusted hazard ratio 1.58 [95% confidence interval [CI], 1.2-2.1]; P=.0012]) found that EGFR ex20ins patients had a 58% greater risk of shorter time to next-line therapy compared with wt-NSCLC. The first ICI line rwTTNT for EGFR ex20ins NSCLC was 3.7 months (95% CI, 3.0-4.9) while for wt-NSCLC it was 5.8 months (95% CI, 5.6-6.0). There was little to no discernible variation in rwOS between the study groups.

Patients with EGFR ex20ins may not benefit as much from ICI treatment as those with wt-NSCLC. Tumors containing ex20ins appear to be less sensitive to immune checkpoint inhibition than wt-NSCLC, which is consistent with previous studies on exon 19 deletion and L858R substitution.