First-line osimertinib in advanced EGFR-mutated NSCLC: real-world outcomes, clinicogenomic correlates, and oligoprogression management in a multicenter Spanish cohort

Cancer research · NSCLC · EGFR · TP53 · osimertinib

In a real-world cohort, first-line osimertinib achieved an objective response rate of 73.5 %, median real-world progression-free survival of 17.5 months, and median real-world overall survival of 28.1 months, but only 50 % of patients who progressed received second-line therapy; oligoprogression occurred in 28 % and local ablative therapy combined with osimertinib was associated with improved progression-free survival.

This retrospective multicenter study evaluated the real-world effectiveness and patterns of progression of first-line osimertinib in 268 patients with EGFR-mutated advanced non‑small-cell lung cancer (NSCLC). 73.5 % achieved an objective response, with a median real-world progression-free survival of 17.5 months and a median overall survival of 28.1 months. Only about half of the patients who progressed received subsequent therapy. Oligoprogression was seen in 28 % of patients, and local ablative therapy (LAT) combined with continued osimertinib improved progression-free survival in exploratory analyses. Re-biopsy at progression identified resistance mechanisms including MET amplification and small-cell transformation.

This study provides the first real‑world evidence of the durability and limitations of first-line osimertinib, highlights significant post-progression attrition, and offers insight into oligoprogressive disease management and resistance mechanisms, informing future therapeutic strategies in EGFR-mutated NSCLC.

Evidence level: Állatkísérletes. Állatmodellben vizsgálták.

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