Efficacy and safety of hetrombopag for secondary prevention of chemotherapy-induced thrombocytopenia in patients with gynecologic malignancies: A single-arm phase 2 trial.

Abstract

e24185 Background: Chemotherapy-induced thrombocytopenia (CIT) is common in patients (pts) with gynecologic malignancies and may cause chemotherapy dose reductions, delays, bleeding, and compromised antitumor efficacy. Pts with prior CIT have a high recurrence risk. However, evidence on secondary prevention of CIT remains limited, especially in gynecologic oncology. This study evaluated the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, for preventing recurrent CIT in pts with gynecologic malignancies. Methods: This single-arm study (NCT06099925) enrolled pts with histologically or cytologically confirmed gynecologic malignancies who had ≥ grade 2 thrombocytopenia in the previous cycle and whose platelet counts (PLT) recovered to ≥ 100 × 10⁹/L through routine interventions before scheduled platinum and/or taxane-based chemotherapy. Based on an 85% historical CIT recurrence rate without prophylaxis, hetrombopag was expected to reduce recurrence to 70%; 43 pts were required (one-sided α = 0.05, 80% power), and 48 were planned allowing for a 10% dropout rate. Pts received oral hetrombopag 5 mg once daily for 10 days, starting within 24 h post-chemotherapy, with dose adjustments based on PLT. The primary endpoint was the proportion of pts with PLT < 75 × 10⁹/L during the chemotherapy cycle in which hetrombopag was administered for prophylaxis. Results: Between October 2023 and June 2025, 43 pts were enrolled. Mean baseline PLT was 209.5 × 10⁹/L (SD 99.6). During the chemotherapy cycle in which hetrombopag was administered for prophylaxis, 37.2% (95% CI, 27.9–61.9) experienced PLT < 75 × 10⁹/L, and the median duration of PLT ≥75 × 10⁹/L was 15.0 days (range 0.0, 22.0). On day 21 after chemotherapy, 74.4% had PLT ≥ 75 × 10⁹/L (95% CI, 73.9–96.9), and 55.8% ≥ 100 × 10⁹/L (95% CI, 49.0–81.4). No platelet transfusions were required, and 14.0% experienced chemotherapy delays. From the initiation of hetrombopag administration to the end of the chemotherapy cycle, mean PLT declined from day 3, nadired on day 15 (124.9 × 10⁹/L, SD 71.4), and partially recovered by day 21 (130.3 × 10⁹/L, SD 76.4). Mean nadir and maximum PLT during this period were 96.3 × 10⁹/L (SD 44.4) and 215.9 × 10⁹/L (SD 89.0), respectively. Compared with the previous chemotherapy cycle, the proportions of pts in each category of nadir PLT were lower during the current cycle (PLT < 25 × 10⁹/L: 0 vs 16.3%; 25–50 × 10⁹/L: 16.3% vs 39.5%; 50–75 × 10⁹/L: 20.9% vs 44.2%). Mean PLT before initiation of the subsequent cycle of antitumor therapy was 123.7 × 10⁹/L (SD 70.9). Hetrombopag was well tolerated, with no treatment-related adverse events. Conclusions: Hetrombopag is safe and may reduce CIT recurrence and severity, decrease platelet transfusion requirements, facilitating timely chemotherapy, representing a convenient option for secondary CIT prevention. Clinical trial information: NCT06099925 .