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Recent advances in EGFR-targeted therapies for non-small cell lung cancer

Luca Lucente1,2, Lucrezia Barcellini1,2, Beatrice Ramella Pollone1,2

  • 1Academic Medical Oncology Unit, AOM - IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Expert Opinion on Pharmacotherapy
|July 23, 2026
PubMed
Abstract

Insights

New strategies combining osimertinib with chemotherapy or bispecific antibodies are improving outcomes for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Risk-stratified, biomarker-driven treatment is key to overcoming resistance and optimizing patient care.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Epidermal growth factor receptor (EGFR) mutations are critical drivers in non-small cell lung cancer (NSCLC).
  • Third-generation tyrosine kinase inhibitor (TKI) osimertinib is the current standard for EGFR-mutated NSCLC, but resistance limits long-term efficacy.
  • Novel combination and sequencing strategies are needed to improve durable responses.

Purpose of the Study:

  • To review recent advancements in EGFR-targeted therapies for NSCLC.
  • To focus on frontline intensification strategies and post-progression treatments for acquired resistance.
  • To discuss the evolving molecular landscape of EGFR mutations.

Main Methods:

  • Comprehensive literature search of PubMed (January 2021-March 2026).
  • Review of major oncology conference proceedings (ASCO, ESMO, WCLC, ELCC).
  • Inclusion of data from clinical trial registries for ongoing studies.

Main Results:

  • Frontline intensification with TKI combinations (chemotherapy or bispecific antibodies) shows promise.
  • Biomarker-driven, risk-stratified approaches are shifting treatment paradigms.
  • High-risk patients benefit significantly from combination regimens.

Conclusions:

  • The therapeutic landscape is moving towards intensified, biomarker-guided treatment for advanced NSCLC.
  • Validating predictive biomarkers, like circulating tumor DNA (ctDNA), is crucial for adaptive strategies.
  • Balancing efficacy, toxicity, cost, and global access is essential for future progress.
Keywords:
AmivantamabEGFRantibody-drug conjugatesivonescimablung cancerosimertinibresistancetargeted therapy

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