Sacituzumab Tirumotecan Improves Survival in EGFR-Mutated Non-Small Cell Lung Cancer
Key Clinical Summary:
- Design/Population: The phase 3 OptiTROP-Lung03 trial randomized 137 patients with advanced EGFR-mutant NSCLC who had progressed after EGFR TKI and platinum-based chemotherapy to receive sacituzumab tirumotecan or docetaxel. Crossover tosacituzumab tirumotecan was permitted.
- Key Outcomes: Sacituzumab tirumotecan significantly improved progression-free and overall survival compared with docetaxel, with consistent benefit after crossover adjustment. Treatment-related adverse events were common but less frequent than with docetaxel, and no interstitial lung disease was reported.
- Clinical Relevance: These findings support sacituzumab tirumotecan as a promising treatment option for patients with EGFR-mutant NSCLC after standard therapies. The magnitude of benefit and manageable safety profile suggest a potential shift in post-TKI treatment strategies.
Updated results from the phase 3 OptiTROP-Lung03 trial demonstrate that sacituzumab tirumotecan, a TROP2-targeting antibody-drug conjugate with a bifunctional linker, significantly improves survival outcomes compared with docetaxel in previously treated patients with EGFR-mutated non-small cell lung cancer (NSCLC).
These results were presented at the European Lung Cancer Congress in Copenhagen, Denmark, by Yunpeng Yang, MD, PhD, Sun Yat-sen University Cancer Center, Guangdong, China.
In this study, 137 patients who experienced disease progression after treatment with an EGFR tyrosine kinase inhibitor and platinum-based chemotherapy were randomized 2:1 to receive either 5 mg/kg of sacituzumab tirumotecan every 2 weeks (n = 91) or 75 mg/m² of docetaxel every 3 weeks (n = 46). Patients in the docetaxel arm were permitted to cross over to receive sacituzumab tirumotecan upon disease progression. Primary end points included progression-free survival (PFS) and overall survival (OS). Secondary end points included crossover-adjusted OS and safety.
At a median follow-up of 23.8 months, median PFS was 7.9 months in the sacituzumab tirumotecan arm and 2.8 months in the docetaxel arm. Median OS was 20 months and 13.5 months, respectively. In the docetaxel arm, 41.3% of patients received sacituzumab tirumotecan as subsequent therapy. After adjusting for crossover, median OS was 20 months in the sacituzumab tirumotecan arm and 11.2 months in the docetaxel arm, with 18-month OS rates of 54.7% and 9.1%, respectively.
Grade ≥3 treatment-related adverse events occurred in 60.4% of patients in the sacituzumab tirumotecan arm and 73.9% of patients in the docetaxel arm. Serious treatment-related adverse events occurred in 20.9% and 41.3% of patients, respectively. No cases of interstitial lung disease were reported in patients who received sacituzumab tirumotecan.
“[Sacituzumab tirumotecan] continues to demonstrate clinically meaningful and significant improvements in PFS and OS compared to docetaxel, with a manageable safety profile in pts with previously treated advanced EGFR-[mutated] NSCLC,” concluded Dr Wengeng et al. “These results underscore [sacituzumab tirumotecan] as a promising new treatment option for this population.”
Source:
Wengeng F, Yunpeng Y, et al. Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC): Final overall survival (OS) analysis from the randomized OptiTROP-Lung03 study. Presented at European Lung Cancer Congress. March 28 - 28, 2026. Copenhagen, Denmark. LBA4.
