Flumonertinib after prior third-generation EGFR-tyrosine kinase inhibitor (TKI) therapy in patients with epidermal growth factor receptor-mutated non-small cell lung cancer after resistance to third-generation tyrosine kinase inhibitor treatment: a real-world study

Background: )-mutated non-small cell lung cancer (NSCLC) due to their exceptional efficacy and favorable safety profile. However, resistance to third-generation TKIs is inevitable. Subsequent treatment options are limited and confer only modest survival benefit. This retrospective study examined patients receiving flumonertinib after prior third-generation EGFR-TKI therapy following resistance to third-generation TKIs, with the aim to assess a potential therapeutic approach for this challenging patient population. Methods: This retrospective study included a cohort of 40 patients who received flumonertinib after prior third-generation EGFR-TKI therapy following resistance to other third-generation TKIs. Kaplan-Meier analysis, Cox proportional hazards regression analysis, and Cox subgroup analysis were employed to examine factors influencing patient survival. Results: The median progression-free survival (PFS) for the overall cohort was 8.95 months, and the median overall survival (OS) was 18.03 months. Patients who received flumonertinib after prior third-generation EGFR-TKI therapy (80 or 160 mg) as first- to third-line therapy (≤3 prior lines of therapy) demonstrated significantly improved survival outcomes [hazard ratio (HR) =0.43, 95% confidence interval (CI): 0.20-0.89; P=0.02]. Cox subgroup analysis further revealed that patients receiving flumonertinib monotherapy derived a significant survival benefit (HR =0.24, 95% CI: 0.07-0.85, P=0.02; P for interaction =0.04). Conclusions: TKIs, flumonertinib monotherapy during rechallenge treatment is a viable therapeutic option. Initiating treatment with flumonertinib earlier may lead to better survival outcomes, and thus further investigation of this strategy is warranted.