Third-generation versus first-generation EGFR tyrosine kinase inhibitors in Asian patients with advanced EGFR mutant non-small cell lung cancer: a meta-analysis of randomized controlled trials.

Abstract

Background: Third-generation EGFR-TKIs (TGETs) have demonstrated improved clinical outcomes compared to first-generation EGFR-TKIs (FGETs) in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Nonetheless, the comparative safety and efficacy of TGETs as a first-line option for Asian patients with advanced EGFR-mutant NSCLC remain unclear. This meta-analysis aims to compare the survival outcomes, response rates, and adverse events (AEs) of TGETs versus FGETs in this population.

Methods: We systematically searched 6 databases for eligible phase 3 randomized controlled trials (RCTs). Eligible studies included those comparing TGETs with FGETs in previously untreated Asian patients with EGFR-mutant advanced NSCLC. Pooled hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) for response rates, and AEs were calculated and analyzed.

Results: Seven phase 3 RCTs comprising 2434 Asian patients were included. TGETs significantly improved PFS (HR: 0.47 [0.42, 0.52], P < 0.00001) and central nervous system-PFS (HR: 0.57 [0.40, 0.80], P = 0.001) compared to FGETs. A trend toward improved OS was also observed with TGETs (HR: 0.88 [0.75, 1.03], P = 0.10). The advantages of PFS in the TGET group were confirmed in all subgroups. The objective response rate (ORR) (RR: 1.05 [1.01, 1.09], P = 0.03) and duration of response (DOR) (HR: 0.41 [0.34, 0.48], P < 0.00001) were also better in the TGET group. Total/grade 3-5 treatment-emergent AEs (TEAEs) and Total/grade 3-5 treatment-related AEs (TRAEs) were similar between the two groups. The top 3 TEAEs of TGET group were diarrhea (31.72%), rash (30.90%), and platelet count decreased (27.97%).

Conclusion: Compared with FGETs, TGETs significantly improve PFS, CNS control, response outcomes, and maintain a comparable safety profile for Asian patients with advanced EGFR-mutated NSCLC.