Afatinib Versus Osimertinib for Non-Small Cell Lung Cancer With Uncommon EGFR Mutations: Real-World Outcomes.
Summary
This multicenter retrospective Japanese study compared afatinib and osimertinib as first-line treatments for advanced or recurrent non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations. Weighted analyses revealed no significant differences in time to treatment failure or overall survival between the two EGFR-TKIs. While afatinib was associated with higher response rates and more frequent adverse events requiring dose reduction, subgroup analyses suggested differential treatment effects based on mutation subtype. Furthermore, subsequent immune checkpoint inhibitor-based regimens showed limited additional benefit.
Analysis
**CLINIQUE**: This multicenter retrospective cohort study provides valuable real-world data on the comparative efficacy of afatinib and osimertinib as first-line treatments for NSCLC with uncommon EGFR mutations, a heterogeneous group with less clear guidelines. The lack of significant difference in overall survival (HR, 1.34; 95% CI, 0.73-2.44) and time to treatment failure (HR, 1.04; 95% CI, 0.61-1.77) suggests overall comparable efficacy. However, subgroup analysis, while requiring prospective validation, indicates that EGFR-TKI selection could be optimized based on mutation subtype (osimertinib for L861X, afatinib for compound mutations), acting as a potential predictive biomarker. These findings could justify prospective clinical trials to validate these subgroup observations and refine treatment strategies. The clinical impact could be medium-term (3-5 years) to guide first-line EGFR-TKI selection and potentially avoid the use of ICIs in second-line if the benefit is limited.