The phase III OptiTROP-Breast01 trial confirms, with longer follow-up, that the antibody-drug conjugate sacituzumab tirumotecan (sac-TMT) extends overall survival compared with chemotherapy in patients with previously treated locally recurrent or metastatic triple-negative breast cancer. The benefit seen at the interim analysis is maintained in the final analysis.
What was known
At the prespecified interim analysis, sac-TMT had already improved progression-free survival versus chemotherapy, with a significant overall survival benefit as well. It remained to be seen whether that advantage would hold with longer follow-up.
What this work adds
A total of 263 patients with previously treated locally recurrent or metastatic triple-negative breast cancer were randomly assigned 1:1 to sac-TMT (130) or chemotherapy (133). Overall survival was a key secondary endpoint. Median follow-up in this final analysis was 29.4 months.
Main results
Median overall survival was 14.7 months (95% CI 12.1-20.1) with sac-TMT and 9.9 months (95% CI 8.6-11.8) with chemotherapy; hazard ratio 0.60 (95% CI 0.45-0.80). At 30 months, 26.8% of patients on sac-TMT were still alive versus 13.2% on chemotherapy, and the benefit was consistent across all subgroups. In the chemotherapy group, 27.8% of patients later received another antibody-drug conjugate; after adjustment for that therapy using the rank-preserving structural failure time model, median overall survival was 14.7 months versus an estimated 9.4 months (HR 0.55; 95% CI 0.39-0.73), and a censoring analysis was consistent (HR 0.59; 95% CI 0.43-0.82). The safety profile was unchanged, with no new signals: the most common grade 3 or higher treatment-related events were neutropenia, leukopenia and anaemia. In exploratory patient-reported outcome analyses, time to deterioration was numerically longer with sac-TMT across the five quality-of-life domains assessed, with the largest differences for fatigue and pain.
What it means
The study reinforces the role of sac-TMT in previously treated advanced triple-negative breast cancer. The survival advantage holds after discounting the effect of part of the control group later receiving another conjugate, something increasingly common in practice. The trial does not compare this drug with other available conjugates nor answer which sequence is optimal.
Reading from the breast unit
For a breast unit, the data inform oncology pharmacy planning and haematological monitoring, since neutropenia and anaemia are the most frequent grade 3 or higher events. They also underline the importance of recording which treatment each patient receives at progression, because that shapes how trial results are read.
Reference: Xu B, Yin Y, Fan Y, Ouyang Q, Song L, Wang X, et al. Sacituzumab tirumotecan versus chemotherapy in previously treated locally recurrent or metastatic triple-negative breast cancer: final overall survival analysis of the Phase III OptiTROP-Breast01. Annals of Oncology, 2026. DOI
