Sequentieel afatinib en osimertinib versus afatinib en chemotherapie bij EGFR-gemuteerd NSCLC: Taiwanese data

BACKGROUND: The optimal treatment strategy for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC)-sequential tyrosine kinase inhibitor (TKI) monotherapies versus upfront combination therapies-remains debated. OBJECTIVE: The Giotrif In Advanced NSCLC Taiwan (GIANT) study evaluated the real-world outcomes of sequential afatinib-based strategies. PATIENTS AND METHODS: This multicenter retrospective cohort study included 733 treatment-naïve patients with American Joint Committee on Cancer stage IIIB-IV NSCLC harboring Del19 or L858R EGFR mutations who received first-line afatinib across seven major Taiwanese medical centers between 2016 and 2024. Patients were stratified by second-line therapy into two groups: afatinib-osimertinib (n = 303) and afatinib-chemotherapy/other lines (n = 430). The primary outcome was overall survival (OS). RESULTS: Sequential afatinib-osimertinib therapy achieved a median OS of 55 months (95% confidence interval [CI] 53.2-66.4) compared to 32.3 months (95% CI 30.3-34.5) with alternative strategies (adjusted hazard ratio 0.43, p < 0.001). Survival benefits were consistent across EGFR mutations and brain metastasis statuses. CONCLUSION: Sequential afatinib-to-osimertinib therapy achieved remarkable OS exceeding 55 months in real-world practice, with outcomes appearing competitive with contemporary combination strategies. These findings support sequential TKI therapy as a durable and effective alternative that warrants prospective validation.