Sacituzumab Tirumotecan in EGFR-TKI-Resistant,

Summary

In a phase 3 randomized trial (n=376), sacituzumab tirumotecan significantly improved progression-free survival (8.3 vs 4.3 months; HR 0.49) and overall survival (HR 0.60; P=0.001) compared with chemotherapy in EGFR–TKI–resistant lung cancer. Grade ≥3 adverse events were common but manageable, with neutropenia most frequent.

Key Findings

• Progression-free survival improved to 8.3 months vs 4.3 months (HR 0.49; 95% CI 0.39–0.62).
• Overall survival favored sacituzumab tirumotecan (HR 0.60; 95% CI 0.44–0.82; P=0.001); 18-month OS 65.8% vs 48.0%.
• Grade ≥3 adverse events occurred in 58.0% vs 53.8%; neutropenia was most common (39.9% vs 33.0%).
• Treatment-related serious adverse events were lower with sac-TMT (9.0%) than chemotherapy (17.6%).

Clinical Implications

For EGFR–TKI–resistant lung cancer, sacituzumab tirumotecan may be prioritized over conventional chemotherapy, with close monitoring for neutropenia and other grade ≥3 toxicities.

Limitations

• Some trial details (eligibility, crossover, stratification factors) are not fully described in the excerpt.
• High rates of grade ≥3 adverse events require careful toxicity management.

Future Directions

Define biomarker-enriched subgroups (e.g., TROP2 expression) and optimize sequencing with other ADCs or targeted agents; evaluate quality-of-life and cost-effectiveness.