Abstract PS1-03-27: Impact of Trastuzumab Emtansine with DoseEscalation on Thrombocytopenia inChinesePatientswithHER2-Positive Breast Cancer: A Multicenter Retrospective Study

Abstract Background: Trastuzumab Emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and emtansine, is an established adjuvant or second-line therapy for HER2-positive breast cancer (BC), widely used in China for both early-stage and advanced HER2-positive BC. Thrombocytopenia represents a common adverse event associated with T-DM1 in Chinese patients, with the incidence of grade ≥3 thrombocytopenia reported as 40.4% in the ELAINA study. This study was designed to investigate the impact of T-DM1 with dose escalation on thrombocytopenia incidence. Method: This multicenter, retrospective study enrolled HER2-positive BC patients treated with T-DM1 between May 2024 and March 2025, all of whom had received at least one prior systemic therapy. Patients were stratified into two cohorts: (1) early-stage disease with residual disease (non-pCR) post-neoadjuvant therapy; (2) advanced-stage disease with progression following prior systemic treatments. T-DM1 dose was escalated in a stepwise manner: 2.4 mg/kg administered in Cycle 1, followed by 3.0 mg/kg in Cycle 2, and culminating in 3.6 mg/kg in Cycle 3. Safety was closely monitored at each dose level, especially for thrombocytopenia. Non-pCR patients received up to 14 cycles of T-DM1, while those with advanced-stage continued treatment until disease progression or unacceptable toxicity. The primary outcome was thrombocytopenia incidence. Data on treatment patterns, adverse events, and clinical efficacy were also collected and analyzed. Result: A total of 46 patients were included (37 non-pCR; 9 advanced). The mean age was 52.8±8.9 years. Five patients (10.9%) with visceral crisis were all in advanced-stage. Prior systemic therapy was reported in all patients. All 37 non-pCR patients received neoadjuvant chemotherapy: 78.4% platinum-based, 13.5% anthracycline-based, and 8.1% other regimens. For advanced breast cancer, Seven and 2 patients received T-DM1 as first and later-line therapy, respectively. The initial dose of all the patients was 2.4 mg/kg. Maximum dose levels were 2.4 mg/kg in 39.1%, 3.0 mg/kg in 17.4%, and 3.6 mg/kg in 43.5% of patients, respectively. The median treatment duration was 75 days (range 7-377). Overall, 4 patients (8.7%) discontinued T-DM1: 3 patients (6.5%) due to disease progression and 1 patient (2.2%) as per physician's advice (unrelated to thrombocytopenia). Thrombocytopenia of any grade occurred in 58.7% of patients, while grade ≥3 thrombocytopenia was observed in 30.4% of patients. Thrombocytopenia of any grade occurred with a median onset of 8 days, while grade ≥3 thrombocytopenia occurred with a median onset of 280 days. Conclusion: T-DM1 dose escalation was well tolerated and effective with a relatively low incidence of grade ≥3 thrombocytopenia. Further prospective studies are warranted to confirm the benefit of initial low-dose T-DM1. Citation Format: M. Wang, M. Huang, X. Zhao, H. Che, J. Li, M. Cheng, S. Aili, X. Zhao, X. Wang, Y. Zou, H. Wang. Impact of Trastuzumab Emtansine with DoseEscalation on Thrombocytopenia inChinesePatientswithHER2-Positive Breast Cancer: A Multicenter Retrospective Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-03-27.