Sacituzumab tirumotecan in previously treated advanced or recurrent endometrial cancer: Results from the phase 3 TroFuse-005/ENGOT-en23/GOG-3095 study

doi:10.1016/s0140-6736(26)02099-4

TroFuse-005

Patient / Population Intervention / Exposure Comparison Outcome

In patients with advanced or recurrent endometrial cancer previously treated with platinum and anti-PD-1/PD-L1 therapy, sacituzumab tirumotecan improved progression-free and overall survival compared with physician's choice of doxorubicin or paclitaxel.

N

776patients

Design

Phase 3 trial (blinding not stated) that randomised 776 patients 1:1 to sacituzumab tirumotecan or treatment of physician's choice (doxorubicin or paclitaxel); patients had advanced or recurrent endometrial carcinoma, including carcinosarcoma, after prior platinum and anti-PD-1/PD-L1 therapy, with up to 3 prior lines; stratified by MMR status, TROP2 expression, prior lines and baseline disease status (NCT06132958).

Endpoint

Dual primary endpoints: progression-free survival by blinded independent central review (BICR) and overall survival. Key secondary endpoint: objective response rate by BICR.

ResultMedian PFS 7.2 months (95% CI 5.6-7.6) with sacituzumab tirumotecan vs 3.9 months (95% CI 3.7-5.3) with physician's choice (HR 0.59, 95% CI 0.50-0.70; 1-sided P<0.0001). Median OS 19.0 months (95% CI 16.1-NR) vs 12.1 months (95% CI 11.0-15.2) (HR 0.68, 95% CI 0.55-0.84; 1-sided P=0.0001). ORR 35.1% vs 17.3%, a difference of 17.8 percentage points (95% CI 11.6-23.9; P<0.00001). Median duration of response 11.1 vs 6.9 months. Grade ≥3 treatment-related adverse events 54.4% vs 41.4%, with anaemia the most common (20.8% vs 13.4%). Discontinuation due to treatment-related adverse events 3.1% vs 4.9%, and treatment-related deaths 0.8% vs 0.8%.

Lorusso D, Martin-Babau J, Backes F, et al. The Lancet. 2026. 10.1016/s0140-6736(26)02099-4

Discussion & critique

In a large randomised phase 3 trial, the antibody-drug conjugate improved both PFS and OS over single-agent doxorubicin or paclitaxel, and the OS gain makes the benefit more than a surrogate result. Median follow-up was only 14.0 months and the upper CI limit for median OS in the experimental arm was not reached, so longer-term survival estimates are still immature. The abstract does not state whether the trial was blinded. PFS was assessed centrally, but grade ≥3 toxicity was more frequent with sacituzumab tirumotecan, and quality of life is described only as maintained, with no figures. The abstract gives no results by the stratification factors, such as MMR status or TROP2 expression, so we cannot tell whether the benefit is consistent across those subgroups.