Authors
Luca Lucente, Lucrezia Barcellini, Beatrice Ramella Pollone, Clara Lidia Filipazzi, Simona Coco, Margherita Puppo, Silvia Marconi, Sara Santamaria, Marco Tagliamento, Giovanni Rossi, Chiara Dellepiane, Elisa Bennicelli, Giulia Barletta, Linda Zinoli, Carlo Genova
Published in
Expert opinion on pharmacotherapy. Jul 23, 2026. Epub Jul 23, 2026.
Abstract
The discovery of epidermal growth factor receptor (EGFR) mutations has deeply reshaped the treatment of non-small cell lung cancer (NSCLC). Throughout the last years, third-generation tyrosine kinase inhibitor (TKI) osimertinib in monotherapy has been the standard of care; however, resistance limits durable responses, necessitating novel combinations and sequencing strategies.
This review discusses recent advances in EGFR-targeted therapies within the molecular landscape of classical and uncommon EGFR mutations, focusing on frontline intensification strategies in metastatic disease - specifically TKI combinations with chemotherapy (FLAURA2) or bispecific antibodies (MARIPOSA) - and emerging post-progression strategies to overcome acquired resistance mechanisms. A comprehensive literature search (January 2021-March 2026) was conducted via PubMed, and recent major oncology conference proceedings (ASCO, ESMO, WCLC, ELCC) and clinical trial registries for ongoing studies.
The therapeutic landscape is shifting from a uniform frontline TKI monotherapy approach toward biomarker-driven, risk-stratified, intensification. High-risk patients (e.g. TP53 co-mutations, L858R) derive significant benefit from combination regimens, whereas mono-TKI remains appropriate for favorable prognostic subgroups. Future progress relies on validating predictive biomarkers - particularly circulating tumor DNA (ctDNA) dynamics - to guide adaptive treatment strategies, balancing efficacy gains against toxicity and costs, while ensuring equitable global access to novel therapies.
PMID:
42489649
Bibliographic data and abstract were imported from PubMed on 23 Jul 2026.
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