Secondary prevention of cancer therapy-induced thrombocytopenia with hetrombopag in breast cancer: a multicenter, randomized, exploratory phase II trial

Abstract Background: Cancer therapy-induced thrombocytopenia (CTIT) is a common complication of anti-tumor therapy, leading to treatment delays or interruptions, increased bleeding risk and compromised outcomes. In the present study, we aimed to evaluate the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, for managing and preventing CTIT in patients with breast cancer. Methods: In this multi-center, randomized phase II clinical trial (NCT05394285), breast cancer patients with platelet counts <50×10⁹/L during anti-tumor treatment (Cycle 1) were enrolled. Those patients were randomly assigned (1:1)to receive either hetrombopag or subcutaneous recombinant human thrombopoietin (rhTPO) until their platelet counts >100×10⁹/L, which was defined as the thrombocytopenia treatment phase (TTP). During the secondary prevention phase (SPP), all cases as self-control received hetrombopag for 14 days starting on day 1 of the subsequent anti-tumor treatment cycle (Cycle 2). The primary endpoint was the response rate of the SPP. Secondary endpoints comprised the response rate of TTP (key secondary endpoint), other platelet-related parameters, and safety outcomes. Results: Between September 2022 and May 2025, 67 patients with breast cancer were enrolled. After excluding one patient who withdrew informed consent, 66 patients were randomized. During the trial, 6 patients discontinued participation in the SPP, the remaining 60 patients constituted the per-protocol set (PPS). The majority of patients in the PPS (n=47) received antibody-drug conjugates (ADCs) treatment. For the primary endpoint, the response rate was 85.0% (51/60) in the PPS, and 89.4% (42/47) among patients receiving ADCs. Regarding the key secondary endpoint during the TTP, the response rates were 87.9% (29/33) in patients receiving hetrombopag and 81.8% (27/33) in those receiving rhTPO. No treatment-emergent severe adverse events were observed. Conclusions: Hetrombopag represents a promising and well-tolerated strategy for the secondary prevention and management of CTIT in breast cancer patients, particularly in patients received ADCs.