Background
Phase 3, open-label, randomized trial at 242 centres in 31 countries/regions. N=776. Advanced or recurrent endometrial carcinoma or carcinosarcoma after platinum chemotherapy and anti-PD-(L)1 (up to 3 prior lines). Sacituzumab tirumotecan (sac-TMT) is a TROP2-directed ADC with a belotecan-derived topoisomerase I payload.
Results
Interventions and follow up: Arm A: sac-TMT 4 mg/kg IV days 1 and 15 q28d (n=386)
Arm B: physician's choice: doxorubicin 60 mg/m2 q3w or paclitaxel 80 mg/m2 days 1, 8, 15 q28d (n=390)
Primary endpoints: PFS (BICR, RECIST 1.1) and OS (ITT)
mFollow up: 14.0 mo (IQR 11.0-16.9)
Results: PFS: median 7.2 mo (95% CI 5.6-7.6) vs 3.9 mo (3.7-5.3); HR 0.59 (0.50-0.70); P<.001
OS: median 19.0 mo (16.1-NR) vs 12.1 mo (11.0-15.2); HR 0.68 (0.55-0.84); P=.0001
Arm B: physician's choice: doxorubicin 60 mg/m2 q3w or paclitaxel 80 mg/m2 days 1, 8, 15 q28d (n=390)
Primary endpoints: PFS (BICR, RECIST 1.1) and OS (ITT)
mFollow up: 14.0 mo (IQR 11.0-16.9)
Results: PFS: median 7.2 mo (95% CI 5.6-7.6) vs 3.9 mo (3.7-5.3); HR 0.59 (0.50-0.70); P<.001
OS: median 19.0 mo (16.1-NR) vs 12.1 mo (11.0-15.2); HR 0.68 (0.55-0.84); P=.0001
Adverse events
Grade ≥3 (any): 69% vs 57%
Serious AEs: 35% vs 32%
Treatment-related deaths: 3 (<1%) vs 3 (<1%)
Specific AE profile: NR in abstract
Serious AEs: 35% vs 32%
Treatment-related deaths: 3 (<1%) vs 3 (<1%)
Specific AE profile: NR in abstract
Conclusions
Sac-TMT significantly improved both PFS and OS over standard single-agent chemotherapy after platinum and immunotherapy in advanced endometrial cancer, with manageable safety.
Key Limitations
Open-label with chemotherapy comparator (doxorubicin/paclitaxel); BICR was masked. Median follow-up 14 mo, so OS maturity and long-term benefit are limited. Higher grade ≥3 AE rate with sac-TMT. Subgroup effects by TROP2 expression and MMR status are not detailed in the abstract. Does not compare with other emerging ADCs or lenvatinib-pembrolizumab.
Clinical Context
Post-platinum/post-immunotherapy endometrial cancer has limited options (single-agent chemotherapy, lenvatinib plus pembrolizumab in pMMR if not given earlier, and other ADCs in selected settings). TroFuse-005 is a positive dual-primary (PFS and OS) phase 3 result for a TROP2 ADC and is expected to inform second/third-line practice pending regulatory review. No approval is cited here.
