Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a detailed safety analysis of the randomized OptiTROP-Breast01 study

Sacituzumab tirumotecan (sac-TMT) is a novel anti-trophoblast cell-surface antigen 2 antibody-drug conjugate and has been approved for second-line and subsequent treatment of metastatic triple-negative breast cancer (TNBC) in China. This post-hoc exploratory study aims to further characterize the safety profile of sac-TMT to inform clinical practice. This analysis was based on the safety set from the OptiTROP-Breast01 study, including all subjects who have received at least one dose of sac-TMT or treatment of physician’s choice (TPC). Frequencies and patterns of the adverse events (AEs) were reported. Particular emphasis was placed on hematologic toxicities (including anemia, neutropenia, thrombocytopenia) and stomatitis, which were defined as key AEs in this study. 262 patients (130 for sac-TMT, 132 for TPC) were included. Median time to the onset of grade 3 or higher key AEs primarily occurred within the first two cycles. Most patients with key AEs in the sac-TMT arm ultimately recovered to grade 2 or lower, typically within 14 days. Efficacy was generally comparable among subgroups with early/late dose reduction (reduction within/after 2 months from treatment initiation), or without dose reduction of sac-TMT. Among patients with treatment duration more than 7 months, the incidence of treatment related AEs (TRAEs), including both any grade and grade 3 or higher TRAEs, decreased over time. Sac-TMT demonstrated a manageable safety profile, with adverse events effectively managed through dose modification and appropriate supportive care without compromising its efficacy. Long-term use of sac-TMT further supports its manageable toxicity profile. NCT05347134. 2022-04-26.