The efficacy and safety of PD-1 inhibitors for EGFR-mutant non-small cell lung cancer after tyrosine kinase inhibitor failure: a retrospective real-world cohort study

BACKGROUND: Acquired drug resistance to various tyrosine kinase inhibitor (TKI) inevitably develops in almost all epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). The present study aimed to evaluate the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for such patients after TKI failure and further explore the subpopulation that exhibited the most benefit. METHODS: A total of 102 EGFR-mutant NSCLC patients who received PD-1 inhibitors after developing resistance to EGFR-TKIs were included in the study. The primary endpoints were progression-free survival (PFS) and grade 3–5 adverse events (AEs), while the secondary endpoints were overall survival (OS), disease control rate (DCR) and subgroup analyses. RESULTS: All the 102 patients received 2 or more lines of immunotherapy. The overall median PFS was 4.95 months [95% confidence interval (CI): 3.91–5.89 months]. The EGFR(L858R) group showed a significant PFS benefit compared with the EGFR(D19) group (6.4 vs. 3.5 months, P=0.002), and likewise for the DCR between the 2 groups (EGFR(L858R) vs. EGFR(D19) group: 84.3% vs. 66.7%, P=0.049). In addition, median PFS in the EGFR(T790M)-negative group (6.47 months) was significantly longer than the EGFR(T790M)-positive group (3.20 months) (P=0.003). The overall OS was 10.70 months (95% CI: 8.92–12.48 months), without a prognostic factor. There was a trend towards improved PFS and OS with combination therapy. The incidence of grade 3–5 treatment-related AEs was 19.6%, while the incidence of grade 3–5 immune-related AEs (irAEs) was 6.9%. Treatment-related AEs were similar in different mutation subtypes. The incidence of grade 3–5 irAEs was higher in the EGFR(D19) group (10.3%) compared with the EGFR(L858R) group (5.9%), and likewise in the EGFR(T790M)-negative group (10%) compared with the EGFR(T790M)-positive group (2.6%). CONCLUSIONS: After EGFR-TKI failure, PD-1 inhibitors provided better survival in advanced NSCLC for the EGFR(L858R) subgroup and EGFR(T790M)-negative subgroup, and there was a trend towards improved outcomes with combination therapy. In addition, toxicity was well tolerated. Our real-world study increased the population size and obtained a similar survival outcome compared from clinical trials.