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

Authors

G Suay, S Cases-Esteban, P Capdevila, A García-Márquez, J Garde-Noguera, P Espinosa-Olarte, M Arnal, S Sandiego-Contreras, F Aparisi-Aparisi, C Escoin-Pérez, P Martín-Martorell, J García, A Blasco-Cordellat, S Blasco-Mollá, J D Benítez-Fuentes, C D Ávila-Andrade, M Borregón, O Juan-Vidal

Published in

ESMO real world data and digital oncology. Volume 13. Pages 100725. Epub Jun 22, 2026.

Abstract

First-line osimertinib is standard for advanced EGFR-mutated non-small-cell lung cancer (NSCLC), but upfront combinations (FLAURA2, MARIPOSA) are reshaping this paradigm. Trial practice gaps and the optimal management of oligoprogressive disease (OPD) remain unclear. We evaluated real-world effectiveness, progression patterns, and the role of local ablative therapy (LAT) in a Western European cohort.
Multicenter retrospective cohort from eastern Spain including patients with advanced EGFR-mutated NSCLC treated with first-line osimertinib. Outcomes were objective response rate (ORR), real-world progression-free survival (rwPFS), real-world overall survival (rwOS) and access to second-line therapy. Prespecified analyses examined exon 19 deletion versus p.Leu858Arg, baseline central nervous system metastases, OPD treated with LAT while continuing osimertinib, re-biopsy at progression, and time toxicity.
Among 268 patients, median age was 72 years, 27.6% had Eastern Cooperative Oncology Group performance status ≥2, and 42.5% had brain metastases. Osimertinib achieved an ORR of 73.5%, rwPFS of 17.5 months, and rwOS of 28.1 months, but only 50.1% of patients who progressed initiated second-line therapy. Among 180 patients with documented progression, 51 (28.3%) had OPD and 82.4% received LAT. Exploratory analyses suggested clinically meaningful improvements in median PFS and median OS versus the overall cohort. Re-biopsy identified resistance mechanisms (e.g. MET amplification, small-cell transformation), and time toxicity measures were modest.
In routine practice, first-line osimertinib shows robust effectiveness but lower rwOS than expected and substantial post-progression attrition. These findings underscore the need for risk-adapted treatment strategies and support prospective evaluation of OPD management approaches, including integration of LAT alongside contemporary systemic options.

PMID:
42383195
Bibliographic data and abstract were imported from PubMed on 01 Jul 2026.

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