N Engl J Med

ESMO 2025: Trop-2–directed antibody-drug conjugate improves survival in EGFR-TKI–resistant NSCLC

October 21, 2025

Sacituzumab tirumotecan (sac-TMT), a Trop-2–targeting antibody–drug conjugate, demonstrated statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS), positioning it as a promising new treatment option for EGFR-mutated non-small cell lung cancer (NSCLC) patients with TKI resistance. These results, which were presented at the European Society for Medical Oncology (ESMO) Congress 2025, may shift the second-line treatment paradigm away from platinum-based chemotherapy

Study details: The phase 3 OptiTROP-Lung04 trial evaluated sac-TMT in patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC who'd progressed after EGFR-TKI therapy. A total of 376 patients were randomized to receive either sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. Primary endpoint: PFS, with OS as a key secondary endpoint.

Results: Sac-TMT significantly improved median PFS (8.3 vs. 4.3 months; hazard ratio [HR], 0.49, 95% confidence interval, 0.39-0.62) and OS (HR, 0.60; P=0.001) compared with chemotherapy. At 18 months, OS was 65.8% with sac-TMT vs. 48.0% with chemotherapy. Grade ≥3 adverse events occurred in 58.0% of sac-TMT patients, most commonly neutropenia, but serious adverse events were less frequent than with chemotherapy.

Source:

Fang, W. et al. (2025, October 19). N Engl J Med. Sacituzumab Tirumotecan in EGFR-TKI–Resistant, EGFR-Mutated Advanced NSCLC. https://www.nejm.org/doi/full/10.1056/NEJMoa2512071