Abstract PS1-03-01: Secondary prevention of cancer therapy-induced thrombocytopenia with hetrombopag in breast cancer: a prospective,multi-center,self-controlled exploratory trial

Abstract Background: Cancer therapy-induced thrombocytopenia (CTIT) is a common complication of anti-tumor therapy and causes treatment delays or interruptions, increased bleeding risk and compromised outcomes. We aimed to evaluate hetrombopag, an oral thrombopoietin receptor agonist that prevented CTIT in breast cancer patients. Methods: In this multi-center, prospective exploratory trial (NCT05394285), breast cancer patients with platelet counts (PLT) < 50×109/L during current anti-tumor treatment cycle (Cycle 1) were enrolled. Those patients were randomized to receive either hetrombopag (7.5 mg daily, n = 30) or subcutaneous recombinant human thrombopoietin (rhTPO, 15000 U daily, n = 30) until their PLT >100×109/L, which was defined as the thrombocytopenia treatment phase (TTP). Eligible patients were scheduled to continue the same anti-tumor regimen in their subsequent treatment cycle (Cycle 2). The secondary prevention phase (SPP) was initiated using a self-controlled design, with prophylactic hetrombopag (7.5 mg/day for 14 days) administration beginning one day after the start of Cycle 2. The primary endpoint was the response rate during the SPP, defined as the proportion of patients meeting all predefined criteria before the next treatment cycle (Cycle 3): 1. no platelet transfusion requirement; 2. no anti-tumor treatment modification (≥20% dose cut, ≥5 days delay, or discontinuation) ; 3. absence of severe thrombocytopenia (PLT <25×109/L, or PLT <50×109/L for ≥7 days). Results: Between Sep 2022 and May 2025, 67 breast cancer patients were enrolled in the study. After excluding 1 patient who withdrew informed consent, 66 patients comprised the full analysis set (FAS). During the trial, 6 patients discontinued participation in the SPP, the remaining 60 patients completed both TTP and SPP, forming the per-protocol (PP) population. In the FAS, 51 (77.3%) patients received antibody-drug conjugates (ADCs) monotherapy, 14 (21.2%) received regimens containing chemotherapy (RCC), and 1 (1.5%) with targeted therapy plus ADC. In the PP population, the response rate in the SPP was 85.0% (51/60). During the TTP, 86.7% (26/30) of patients in the hetrombopag group achieved response, compared to 80% (24/30) in the rhTPO group. No treatment-emergent severe adverse events occurred. Conclusions: As the first prospective trial to evaluate hetrombopag for preventing CTIT in breast cancer patients, this self-controlled exploratory study demonstrated hetrombopag may be a promising option for the secondary prevention of CTIT. The promising response rate observed during the TPP, coupled with a favorable safety profile, supports further large-scale investigation of hetrombopag for the prevention of CTIT in multi-cycle anticancer regimens. Citation Format: H. Sun, H. Lv, W. Chen, Y. Zhao, M. Zhang, L. Niu, Z. Liu, X. Guo, X. Chen, Y. Feng, L. Wang, H. Zeng, J. Wang, Y. Cui, M. Yan. Secondary prevention of cancer therapy-induced thrombocytopenia with hetrombopag in breast cancer: a prospective,multi-center,self-controlled exploratory trial [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 PS1-03-01.