Hetrombopag for thrombocytopenia induced by concurrent or sequential chemoradiotherapy in patients with solid tumors: a double-cohort trial

Chemoradiotherapy-induced thrombocytopenia (CRT-IT) is a common and clinically significant complication in cancer patients, yet there are no severity-based treatment guidelines, and existing therapies are limited by safety concerns and practicality. This study aimed to evaluate the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, for the treatment of CRT-IT, and to explore individualized strategies based on the severity of CRT-IT. This prospective, dual-cohort study enrolled adult cancer patients with CRT-IT. Cohort 1 (baseline platelet count [PLT] 30–50 × 10⁹/L) received hetrombopag (initial dose 5 mg or 7.5 mg orally once daily, for up to 14 days with dose adjustments as needed) plus recombinant human interleukin-11 (rhIL-11, 25–50 µg/kg subcutaneously once daily for 7–14 days). Cohort 2 (baseline PLT 50–75 × 10⁹/L) received hetrombopag monotherapy, with the same dosing regimen. Treatment was discontinued once PLT reached ≥ 100 × 10⁹/L or increased by ≥ 50 × 10⁹/L from baseline. The primary endpoints were the proportion of patients achieving PLT recovery to ≥ 75 × 10⁹/L and the median time to recovery. Between March 2022 and June 2024, 28 patients were enrolled. In Cohort 1 (n = 10), six patients (60.0%) achieved PLT recovery to ≥ 75 × 10⁹/L, with a median time of 4.5 days (95% confidence interval [CI]: 2.0–not reached [NR]). In Cohort 2 (n = 18), 14 patients (77.8%) reached this threshold within a median time of 4.5 days (95% CI: 3.0–7.0). One patient from each cohort required rescue therapy (10.0% in Cohort 1; 5.6% in Cohort 2). Grade ≥ 3 treatment-emergent adverse events occurred in one patient per cohort (10.0% in Cohort 1; 5.6% in Cohort 2), but were not attributed to hetrombopag. Hetrombopag, either as monotherapy or in combination with rhIL-11, demonstrated preliminary evidence of effectively and rapidly improving PLT in patients with CRT-IT, with an acceptable safety profile. As an oral agent, monotherapy may offer a convenient option for moderate thrombocytopenia, while combination therapy may be considered for more severe cases. These findings are based on a small, exploratory study, and further validation in larger, controlled trials is warranted. This trial was registered with chictr.org.cn under the identifier ChiCTR2500099546 on 25 March 2025.