Targeting MET-mediated TKI resistance in EGFR-mutant NSCLC
Mené en Chine sur 211 patients ayant reçu un traitement par inhibiteur de tyrosine kinase anti-EGFR pour un cancer avancé du poumon non à petites cellules avec mutation du gène EGFR et amplification du gène MET, cet essai multicentrique de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'une chimiothérapie standard à base d'un doublet de sels de platine par rapport à un traitement combinant savolitinib et osimertinib
The management of advanced non-small-cell lung cancer (NSCLC) with activating mutations in EGFR has evolved over the past 20 years. Whether used alone, or in combination with chemotherapy or the bispecific anti-EGFR MET antibody amivantamab, third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, are the backbone of treatment. Repeat tissue biopsies following progression on EGFR TKIs identify targetable genomic and histological changes driving TKI resistance in a subset of patients. MET gene amplification is one of the most commonly observed resistance mechanisms, occurring in approximately 17–24% of osimertinib-resistant biopsies.1 MET-mediated TKI resistance can be successfully targeted in the clinic; several single-arm studies have shown that adding a selective MET inhibitor, such as savolitinib or tepotinib, to osimertinib yields objective response rates over 50%.2–4 However, until now there have been no randomised trials comparing this personalised approach to standard second-line therapy in advanced EGFR-mutant NSCLC.
The Lancet , commentaire, 2026