Real-World Effectiveness of Hetrombopag for Cancer Therapy-Induced Thrombocytopenia in Cancer Patients
Authors: Liu Yuan , Liu Bo , Zhao Runsheng , Fang Shanshan , Li Lin , Qi Huixiong , Li Quan 
Published: December 2024

Background: Cancer therapy-induced thrombocytopenia (CTIT) is a prevalent hematological complication in patients undergoing cytotoxic chemotherapy for cancer. CTIT can cause an increased risk of bleeding and lead to dose reductions, treatment interruptions or delays, adversely impacting overall survival with a raised medical burden. In recent years, thrombopoietin receptor agonists (TPO-RAs) have been developed and quickly advanced to clinical trials, demonstrating promising therapeutic effects for CTIT. Hetrombopag is an oral, small molecule, synthetic non-peptide TPO-RA that binds to the transmembrane domain of TPO receptors, complementing the function of autologous TPOs. Its effect of treating CTIT in real-world settings, however, remains limited.

Aims: We carried out a retrospective observational study to evaluate the effect of hetrombopag treating cancer therapy-induced thrombocytopenia in real world practice.

Methods: This study included patients with advanced solid tumors undergoing anti-tumor therapy and received at least one dose of hetrombopag at Xiangyang Central Hospital between February 2022 and September 2023. The primary endpoint was the overall response rate to hetrombopag, defined as the percentage of patients achieving a platelet count of ≥75×109/L or an increase from baseline by ≥50 × 109/L, without platelet transfusions, after hetrombopag's treatment.

Results: A total of 110 patients were included in the analysis. The median age was 58.5 years (range: 33-80 years), with 45 patients (40.9%) over 60 years old. Sixty-two patients (56.4%) were female. Tumor types included gastrointestinal tumors in 46 patients (41.8%) , gynecological tumors in 32 patients (29.1%), and lung cancer in 14 patients (12.7%). Eighty patients (72.7%) were in clinical stage 3 or higher. Regarding anti-tumor treatment regimens, 44 patients (40.0%) received chemotherapy alone, 34 patients (30.9%) received chemotherapy combined with other treatments, and 32 patients (29.1%) received other treatments. The median baseline platelet count was 58×109/L (range: 3-108×109/L).

Fifty-eight patients (52.7%) received an initial dose of 7.5mg/ day, 47 patients (42.7%) received an initial dose of 5mg/ day, and 5 patients (4.5%) received an initial dose of hetrombopag of 2.5mg/ day. Sixty-four patients (58.15%) received hetrombopag combined with rh-IL-11 or rh-TPO.

The overall response rate to hetrombopag was 83.33% (90/108). The median time required for patients to achieve platelet counts ≥100×109/L or an increase in platelet count from baseline by ≥50×109/L was 9 days (range: 7-11 days). Twenty-five percent of patients achieved platelet counts ≥100×109/L or an increase in platelet count from baseline by ≥50×109/L within 5 days (range: 5-7 days). Patients' baseline platelet counts were categorized as follows: 75 to 100×109/L, 50 to 75× 109/L, 25 to 50×109/L, and less than 25×109/L. The 14-day response rates were 91.3% (21/23), 84.1% (37/44), 64.0% (16/25), and 56.3% (9/16), respectively.The 28-day response rates were 95.7% (22/23), 90.9% (40/44), 76.0% (19/25), and 56.3% (9/16), respectively.

Conclusion: The results of this study suggest that under real world conditions, oral hetrombopag monotherapy and combinations with rh-IL-11 or rh-TPO are effective treatment options for CTIT, demonstrating high response rates and a short time to recovery in a mixed patient population. These findings are hypothesis-generating and need confirmation in randomized trials in the future.