Sacituzumab Tirumotecan in EGFR-TKI-Resistant, EGFR-Mutated Advanced NSCLC
Mené sur 376 patients atteints d'un cancer du poumon non à petites cellules avec mutation EGFR et de stade avancé ou métastatique (durée médiane de suivi : 18,9 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du sacituzumab tirumotécan après l'échec d'un traitement par inhibiteurs de l'EGFR
Background: Sacituzumab tirumotecan (sac-TMT) is an antibody–drug conjugate targeting trophoblast cell-surface antigen 2 that has shown significant survival benefits in patients with EGFR-mutated non–small-cell lung cancer (NSCLC) that has progressed after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy.
Methods: In this phase 3 trial, we enrolled patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after EGFR-TKI therapy. The patients were randomly assigned, in a 1:1 ratio, to receive sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. The primary end point was progression-free survival as assessed by blinded independent review. Overall survival was a hierarchically tested key secondary end point. In the interim analysis of progression-free survival as assessed by blinded independent review, sac-TMT monotherapy met the prespecified criterion for significance (two-sided P<0.0001); we report here the prespecified final analysis of progression-free survival and the preplanned interim analysis of overall survival.
Results: Overall, 376 patients underwent randomization, with 188 assigned to each group. After a median follow-up of 18.9 months, the median progression-free survival was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group (hazard ratio for disease progression or death, 0.49; 95% confidence interval [CI], 0.39 to 0.62). Overall survival was significantly longer with sac-TMT than with chemotherapy (hazard ratio for death, 0.60; 95% CI, 0.44 to 0.82; two-sided P=0.001); 18-month overall survival was 65.8% and 48.0%, respectively. Treatment-related adverse events of grade 3 or higher occurred in 58.0% of patients receiving sac-TMT and in 53.8% of those receiving chemotherapy, with the most common being a decreased neutrophil count (39.9% vs. 33.0%); treatment-related serious adverse events occurred in 9.0% and 17.6%, respectively.
Conclusions: In patients with EGFR-mutated advanced or metastatic NSCLC that had progressed after previous EGFR-TKI therapy, progression-free survival and overall survival outcomes were significantly better with sac-TMT than with platinum-based chemotherapy. (Funded by Sichuan Kelun-Biotech Biopharmaceutical; OptiTROP-Lung04 ClinicalTrials.gov number, NCT05870319.)
New England Journal of Medicine , résumé, 2025