Retrospective real-world associations between EGFR alterations and furmonertinib outcomes in advanced non-small cell lung cancer.

Abstract

Background: Furmonertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown promising efficacy in EGFR-mutant non-small cell lung cancer (NSCLC). This real-world study aimed to explore efficacy differences among EGFR mutation subtypes and the influence of concomitant genetic alterations on furmonertinib.

Methods: This retrospective multicenter real-world study enrolled patients with unresectable stage IIIB/C-IV EGFR-mutant NSCLC who received furmonertinib (80 milligrams per day). Main eligibility criteria included advanced EGFR-mutant NSCLC, measurable lesions, and available next-generation sequencing (NGS) molecular data. Patients were recruited from five Chinese medical centers. Progression-free survival (PFS) was defined as time from furmonertinib initiation to disease progression or any-cause death; overall survival (OS) was defined as time from furmonertinib initiation to any-cause death or last follow-up. Baseline clinical and NGS-detected molecular data were collected. Survival endpoints included objective response rate (ORR), disease control rates (DCRs), PFS and OS. Kaplan-Meier and Cox proportional-hazards models were applied to evaluate prognostic associations, reporting hazard ratios (HR) with 95% confidence intervals (CIs) alongside exact P values.

Results: A total of 139 patients were included, among whom 64 harbored EGFR exon 19 deletion and 74 harbored L858R mutation. TP53 mutations were detected in 64.4% (58/90) of the tested patients. There were 136 patients profiled for additional concurrent driver alterations. Among 131 evaluable patients, ORR was 69.5% and the DCR was 97.7%. Median PFS of the entire cohort was 623 days (approximately 20.8 months); median OS was not reached. Compared with L858R, EGFR exon19 deletion was associated with longer PFS (adjusted HR =1.77, 95% CI: 1.09-2.87, P=0.02). After adjusting for age, disease stage, and EGFR mutation subtype, multiple gene mutations were associated with poorer PFS (HR =4.03, 95% CI: 1.98-8.19, P<0.001) and OS (HR =3.25, 95% CI: 1.07-9.86, P=0.04). No significant prognostic association was observed for TP53 co-mutation.

Conclusions: This retrospective real-world cohort suggests that EGFR subtypes and multiple concurrent genomic alterations are associated with survival outcomes under furmonertinib treatment.