The efficacy and safety of thrombopoietin receptor agonists in solid tumors with chemotherapy-induced thrombocytopenia: a systematic review and network meta-analysis of randomized controlled trials

Yingyu LaiQianni PanShiyu WangQingmao LuoZhencong HuangMingzhong WeiZhouqian JiangWenyan Yi^*

• Hezhou People's Hospital, Hezhou, China

Objective: The objective of this study is to compare and rank the efficacy and safety of different thrombopoietin receptor agonists (TPO-RAs) in the treatment of chemotherapy-induced thrombocytopenia (CIT) among patients with solid tumors. Methods: PubMed, Cochrane Library, Embase, MEDLINE, Web of Science, ClinicalTrials.gov, CNKI, Wanfang Database, VIP Database, SinoMed, and China Drug Trials (www.chinadrugtrials.org.cn) were searched for randomized controlled trials (RCTs) of TPO-RAs for CIT in solid tumors from inception to December 31, 2024. Cochrane Risk of Bias Assessment tool 2 was used for assessing risk of bias. We performed a random-effects network meta-analysis using STATA 14.0 software. Treatments were ranked according to the surface under the cumulative ranking curve. Confidence of the evidence was assessed using Confidence in Network Meta-Analysis. The study protocol was registered with PROSPERO, number CRD42024612536. Results: A total of 8 studies (568 patients) were included. Most RCTs (7/8) showed a low risk of bias. The confidence in evidence was often low or very low. Our network meta-analysis indicate that when compared with placebo, hetrombopag (summary RR 0.45, 95% confidence interval 0.28 to 0.73) and eltrombopag (0.57, 0.41 to 0.81) significantly reduced the incidence of chemotherapy dose reduction or delay due to thrombocytopenia. Hetrombopag (0.29, 0.13 to 0.68) also significantly reduced the platelet transfusions. Eltrombopag had the lowest risk for bleeding event (0.41, 0.13 to 1.23) and mortality (0.83, 0.48 to 1.44). There were no significant differences in the risk of AEs between interventions. Hetrombopag (0.37, 0.02 to 8.68) showed the least risk of thrombosis. According to rankograms, hetrombopag was ranked as the best for reducing the incidence of chemotherapy dose reduction or delay, and platelet transfusions, with the least risk of serious AEs and thrombosis. Eltrombopag carried the least risk of bleeding events and mortality. Conclusion: Our network meta-analysis suggested that based on the limited indirect data, hetrombopag may represent the perferred therapy for avoiding chemotherapy dose reductions or delays and platelet transfusion. Eltrombopag may be considered the preferred therapeutic option for avoiding the bleeding events and mortality. Both them have acceptable safety profile. However, larger head-to-head trials are needed to confirm these findings.