Sacituzumab tirumotecan improved survival for patients with EGFR TKI–resistant, EGFR‐mutant advanced NSCLC

CANCERT he TROP2-targeting antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) significantly improved progression-free survival (PFS) and overall survival (OS) in comparison with pemetrexed plus platinum-based therapy in patients with EGFR-mutated non-small cell lung cancer (NSCLC) that had progressed after an EGFR tyrosine kinase inhibitor (TKI) according to the results of the OptiTROP-Lung04 trial. 1 These findings, which were presented at the 2025 European Society for Medical Oncology Congress by Li Zhang, MD, an oncologist at the Guangdong Provincial Clinical Research Center for Cancer in Guangzhou, China, and were published simultaneously in The New England Journal of Medicine, confirmed the findings from an earlier phase 2 trial of sac-TMT, which showed significant improvements in PFS and OS in comparison with docetaxel. 2 The phase 3 trial enrolled 376 patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after a prior EGFR TKI (94.7% of the patients had received a third-generation EGFR TKI).Patients were randomly assigned to sac-TMT or pemetrexed plus platinum-based chemotherapy.The trial enrolled only Asian patients.The final PFS analysis showed a 4-month improvement in median PFS with sac-TMT in comparison with chemotherapy (8.3 vs. 4.3 months; hazard ratio [HR], 0.49; 95% CI, 0.39-0.62).A preplanned interim OS analysis that was conducted at a median follow-up of 18.9 months showed a 40% reduction in the risk for death with sac-TMT versus chemotherapy (HR, 0.60; 95% CI, 0.44-0.82;two-sided p = .001).The median OS was not reached for patients on sac-TMT but was 17.4 months for patients on chemotherapy.The OS rate at 18 months was 65.8% for patients on sac-TMT and 48.0% for patients on chemotherapy.The majority of the patients who discontinued the trial went on to have subsequent anticancer treatment.Approximately half of the patients in the sac-TMT arm (41.9%) and the chemotherapy arm (53.6%) had subsequent chemotherapy.Subsequent ADCs were given to 1.4% of the patients assigned to sac-TMT and to 19.6% of the patients assigned to chemotherapy.The rates of grade 3 or higher treatment-related adverse events were similar for sac-TMT (58.0%) and chemotherapy