Multiple standards of care in non-small-cell lung cancer after EGFR-TKI therapy: progress, fragmentation, or inevitability?
Mené sur 498 patients atteints d'un cancer du poumon non à petites cellules avec mutation EGFR, de stade localement avancé ou métastatique et ayant progressé après un traitement par inhibiteur de tyrosine kinase ciblant EGFR (âge médian : 60 ans ; durée médiane de suivi : 7,7 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du ruzaltatug rézétécan (un conjugué anticorps-médicament ciblant HER3) par rapport à une chimiothérapie à base de sels de platine
The treatment landscape of EGFR-mutated non-small-cell lung cancer harbouring exon 19 deletion or L858R mutations has advanced remarkably over the past two decades. Although acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is inevitable in most patients, novel compounds such as bispecific antibodies and antibody–drug conjugates (ADCs) have expanded the armamentarium of options after EGFR-TKI therapy. Following the global MARIPOSA-2 trial that showed superior progression-free survival (PFS) of amivantamab plus platinum–pemetrexed chemotherapy over platinum–pemetrexed chemotherapy alone in patients who have progressed on osimertinib,1 this is the second-line option preferred by major guidelines including the National Comprehensive Cancer Network and the European Society for Medical Oncology.2 TROP2-directed ADCs have also demonstrated activity and datopotamab deruxtecan has received US Food and Drug Administration (FDA) approval for use in patients who have received previous EGFR-directed therapy and platinum-based chemotherapy based on the pooled analyses of two trials,3 although neither was conducted exclusively in the EGFR-mutant population. Sacituzumab tirumotecan (sac-TMT), another TROP2-directed ADC, has obtained regulatory approval by China's National Medical Products Administration (NMPA) in the second-line and third-line setting following two China-only randomised trials that demonstrated superior PFS and objective response rates over platinum–pemetrexed and docetaxel chemotherapy, respectively.
The Lancet , commentaire, 2026