Detailed safety analysis shows sacituzumab tirumotecan manageable in metastatic triple-negative breast cancer

A detailed, post-hoc safety analysis of the randomized phase 3 OptiTROP-Breast01 trial has found that sacituzumab tirumotecan, a novel antibody-drug conjugate approved in China for previously treated metastatic triple-negative breast cancer, produced adverse events that were concentrated early in treatment, largely reversible, and manageable through dose modification and supportive care. The analysis, published in Breast Cancer Research, examined 262 patients and placed particular emphasis on hematologic toxicities—anemia, neutropenia, and thrombocytopenia—and stomatitis, which together accounted for most grade 3 or higher treatment-related adverse events in the sacituzumab tirumotecan arm.

Of 263 enrolled patients, one assigned to the chemotherapy arm received no study treatment and was excluded, leaving a safety set of 130 patients on sacituzumab tirumotecan and 132 on physician’s choice. Among control-arm patients, 66.67 percent received eribulin, 15.15 percent gemcitabine, 15.15 percent vinorelbine, and 3.03 percent capecitabine.

The treated population was heavily pretreated: the median number of previous chemotherapy lines in the advanced setting was 3 in the sacituzumab tirumotecan arm and 2 in the control arm, with a range of 2 to 6. The median age was 51 years, all patients were female, and most had an Eastern Cooperative Oncology Group performance status score of 1. Median exposure was 24.9 weeks for sacituzumab tirumotecan versus 8.6 weeks for chemotherapy, and the median relative dose intensity was 89.5 percent versus 95.5 percent.

Overall treatment-related adverse event profiles were broadly comparable between arms. All patients treated with sacituzumab tirumotecan experienced a treatment-related adverse event of any grade, with grade 3 or 4 events in 63.1 percent; in the control arm, 96.2 percent had events of any grade and 56.8 percent had grade 3 or higher events. Dose modifications were more frequent with sacituzumab tirumotecan: dose reductions occurred in 30.8 percent of patients versus 15.9 percent, and treatment interruptions in 56.2 percent versus 40.9 percent. Treatment-related adverse events led to discontinuation in 1.5 percent of patients in both arms. One fatal treatment-related adverse event, multiple organ dysfunction syndrome, occurred in the sacituzumab tirumotecan arm; the investigators attributed the death after a single dose to confounding factors including pre-existing COVID-19 infection, rapid tumor progression, and liver failure due to acute cholecystitis.

The key adverse events showed distinct patterns. Treatment-related anemia was more frequent with sacituzumab tirumotecan than chemotherapy, at 82.3 percent versus 54.5 percent of any grade and 29.2 percent versus 6.1 percent at grade 3 or higher. Median time to onset of grade 3 or higher anemia was 36.5 days versus 45 days. Medical management of anemia was required in 24.6 percent of sacituzumab tirumotecan patients, including erythropoietin in 23.8 percent and transfusions in 2.3 percent. Among patients with grade 3 or higher anemia, 36 of 38 in the sacituzumab tirumotecan arm recovered to grade 2 or lower, with a median recovery time of 7 days. Neutropenia of any grade was similar between arms at 78.5 percent versus 74.2 percent, but grade 3 or higher neutropenia was lower with sacituzumab tirumotecan, at 34.6 percent versus 47 percent, and febrile neutropenia was rare, occurring in 1.5 percent versus 3.0 percent of patients.

Thrombocytopenia was also more frequent with sacituzumab tirumotecan, at 40.8 percent versus 25.8 percent of any grade and 13.1 percent versus 3.8 percent at grade 3 or higher, with a median onset of grade 3 or higher events at 12 days versus 15 days. Stomatitis showed the largest contrast: any-grade stomatitis occurred in 49.2 percent of sacituzumab tirumotecan patients versus 4.5 percent on chemotherapy, and grade 3 or higher stomatitis in 10.0 percent versus 0.8 percent. Across all four key adverse events, the median time to onset of grade 3 or higher events fell primarily within the first two treatment cycles, and most affected patients in the sacituzumab tirumotecan arm recovered to grade 2 or lower, typically within 14 days. No key adverse event led to treatment discontinuation or death in either arm.

Supportive care use reflected these patterns. Granulocyte colony-stimulating factor was given as secondary prophylaxis in 25.4 percent of sacituzumab tirumotecan patients and 39.4 percent of control patients, and as treatment for neutropenia in 47.7 percent versus 62.1 percent, with use declining in both arms as treatment cycles progressed. For stomatitis, 4.6 percent of sacituzumab tirumotecan patients received prophylaxis and 30.8 percent received symptomatic treatment. Other adverse events associated with unrelated antibody-drug conjugates were uncommon: diarrhea was reported in 13.1 percent of sacituzumab tirumotecan patients, nearly all grade 1 or 2; grade 2 interstitial lung disease in one patient; xerophthalmia in 2.3 percent; and grade 3 or higher infusion-related reactions or hypersensitivity in 1.5 percent. Grade 3 or higher elevations in alanine or aspartate aminotransferase remained below 2.5 percent.

Among 97 remaining patients, 18 had an early dose reduction, 20 a late dose reduction, and 59 no dose reduction. Median progression-free survival was 5.2, 6.5, and 6.0 months in the three groups respectively, and median overall survival was 7.5, 12.3, and not reached. The differences were modest and numerical, and the authors cautioned that the small subgroup sizes and possible effects of subsequent therapies limit interpretation. A sensitivity analysis based on relative dose intensity during the first two months similarly showed only slight numerical differences in progression-free survival, 6.3 versus 5.2 months. Overall, the data suggest that dose modification for adverse event management did not appear to compromise efficacy, though the timing of dose reduction may remain clinically relevant and requires validation.

Long-term use also appeared tolerable. Among 50 patients treated for at least seven months, the incidence of both any-grade and grade 3 or higher treatment-related adverse events declined over time, with grade 3 or higher events dropping notably from cycle 2 and remaining consistently low from cycle 4 onward, and no additional late-onset events were identified. Hematologic toxicity was also generally consistent across subgroups defined by prior lines of therapy, with grade 3 or higher treatment-related adverse events reported in 48.4 percent of patients previously treated with two lines and 45.6 percent of those with three or more lines.

The authors emphasized the limitations of the work. It was a post-hoc, exploratory analysis of a clinical trial population of heavily pretreated Chinese women, and the small sample sizes after subgrouping mean the findings require confirmation in larger prospective trials and in broader real-world populations. Nevertheless, the analysis offers a practical message for clinicians using sacituzumab tirumotecan: grade 3 or higher hematologic toxicities and stomatitis arise chiefly within the first two cycles, consistent with prescribing information recommending weekly blood count monitoring during the first two months of treatment, and most such events recover to grade 2 or lower within about two weeks when managed with dose interruption, dose reduction, and supportive care.

Subject of Research: Safety profile of the antibody-drug conjugate sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer

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

Article References: Fan, Y., Ouyang, Q., Yin, Y., Song, L., Wang, X., Li, W., Li, M., Yan, X., Wang, S., Sun, T., Teng, Y., Tang, X., Tong, Z., Sun, Z., Ge, J., Jin, X., Diao, Y., Liu, G., & Xu, B. (2026). Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a detailed safety analysis of the randomized OptiTROP-Breast01 study. Breast Cancer Research, 28(1), Article 163. https://doi.org/10.1186/s13058-026-02339-z

Image Credits: AI Generated

DOI: 10.1186/s13058-026-02339-z

Keywords: sacituzumab tirumotecan, triple-negative breast cancer, antibody-drug conjugate, OptiTROP-Breast01, hematologic toxicity, stomatitis, neutropenia, anemia, thrombocytopenia, dose reduction, TROP2, phase 3 trial