ArticleDiscover oncology2025
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.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThird-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.
methodsWe 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.
resultsSeven 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%).
conclusionCompared with FGETs, TGETs significantly improve PFS, CNS control, response outcomes, and maintain a comparable safety profile for Asian patients with advanced EGFR-mutated NSCLC.
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