A detailed safety analysis of the phase III, multicenter, open-label, randomized, controlled OptiTROP-Breast01 trial suggests that sacituzumab tirumotecan (sac-TMT) has a manageable safety profile and that adverse events (AEs) can be effectively managed through dose modification and appropriate supportive care without compromising its efficacy in previously treated metastatic triple-negative breast cancer (mTNBC).
sac-TMT is a novel anti-trophoblast cell-surface antigen 2 antibody–drug conjugate, which was approved in China for second- and subsequent-line treatment of metastatic TNBC on the basis of the OptiTROP-Breast01 trial that evaluated sac-TMT vs treatment of physician’s choice (TPC). [Nat Med 2025;31:1969-1975]
A total of 262 patients (median age, 51 years; female, 100 percent) were included in the safety analysis set. In the TPC arm (n=132), eribulin, gemcitabine, vinorelbine, and capecitabine were given to 66.67, 15.15, 15.15, and 3.03 percent of patients, respectively. Baseline patient characteristics were well balanced between the two arms. The median number of previous chemotherapy lines was 3 for the sac-TMT group and 2 in the TPC arm (range, 2–6 for both). [Breast Cancer Res 2026;28:163]
The median duration of exposure was 24.9 weeks for sac-TMT and 8.6 weeks for TPC. Grade ≥3 AEs occurred in 63.1 and 56.8 percent of patients on sac-TMT and TPC, respectively. The sac-TMT group had a higher frequency of dose modifications, with dose reductions required in 30.8 percent of patients vs 15.9 percent in the TPC arm. Treatment interruptions were also more frequent with sac-TMT (56.2 vs 40.9 percent). One fatal TRAE (multiple organ dysfunction syndrome) occurred in the sac-TMT arm, while there were no fatal TRAEs in the TPC arm.
Most patients who experienced grade ≥3 key AEs in the sac-TMT arm ultimately recovered to grade ≤2, with most achieving recovery within 14 days. Treatment-related AEs (TRAEs) led to treatment discontinuation in 1.5 percent of patients in each arm.
Among grade ≥3 TRAEs, haematologic toxicities and stomatitis were the most common and defined as key AEs. With the exception of grade ≥3 neutropenia (34.6 vs 47.0 percent), anaemia (29.2 vs 6.1 percent), thrombocytopenia (13.1 vs 3.8 percent), and stomatitis (10.0 vs 0.8 percent) of grade ≥3 were all more prevalent with sac-TMT vs TPC.
Erythropoietin was required for management of anaemia in 23.8 vs 3.8 percent of patients and blood product transfusions were needed in 2.3 vs 1.5 percent of patients on sac-TMT vs TPC. Granulocyte colony–stimulating factor was given as treatment for neutropenia in 47.7 vs 62.1 percent of patients in the sac-TMT vs TPC arms. Recombinant human thrombopoietin was administered to 10.8 vs 6.1 percent of patients for managing thrombocytopenia in the sac-TMT vs TPC group, while 30.8 percent of patients on sac-TMT received symptomatic treatment for stomatitis, including medications for oral lesions and ulcers.
The median time to onset of grade ≥3 key AEs indicated that these events primarily occurred within the first two cycles. “Therefore, closer monitoring of haematologic toxicities is essential during the first 2 months of administration,” stressed the researchers.
Patients in the early dose reduction group had numerically shorter progression-free survival PFS and overall survival than patients without dose reduction and those with late dose reductions. “One possible explanation is that early dose reduction may reduce dose intensity, leading to insufficient drug exposure and potentially less effective tumour control. However, the numerical differences were modest,” noted the researchers.
“Overall, the available data suggest that dose modification for AE management did not appear to compromise the efficacy of sac-TMT,” they concluded.