Hematologic toxicities of sunitinib in patients with gastrointestinal stromal tumors: a systematic review and meta-analysis

Purpose Sunitinib offers a significant survival benefit to patients with imatinib-resistant gastrointestinal stromal tumors (GIST). However, the incidence and risk of sunitinib-induced hematologic toxicities in such a population are often overlooked and have not been well characterized. This meta-analysis was performed to assess the summary incidence and risk of hematologic toxicities secondary to sunitinib in patients with GIST. Methods Searches were performed in PubMed, Embase, Cochrane Library, and Web of Science as well as ClinicalTrials.gov to identify relevant studies up to April 2022. Studies with adequate safety profile, including anemia, neutropenia, and thrombocytopenia, were included to calculate the pooled incidence, relative risk (RR), and corresponding 95% confidence intervals (CIs). This study was registered with PROSPERO under number CRD42022328202. Results A total of 2593 patients from 13 studies were included in the present meta-analysis. For patients with GIST assigned to sunitinib, the overall incidences of all-grade anemia, neutropenia, and thrombocytopenia were 26.2% (95% CI, 14.9–39.4%), 41.8% (95% CI, 29.0–55.1%), and 36.4% (95% CI, 22.8–51.1%), respectively. Regarding high-grade (grades 3 and 4) events, there were 4.7% (95% CI, 3.8–5.6%) for anemia, 9.3% (95% CI, 5.6–13.7%) for neutropenia and 5.0% (95% CI, 2.9–7.3%) for thrombocytopenia. Compared to placebo arms, sunitinib was related to an increased risk of high-grade neutropenia with an RR of 10.39 (95% CI, 1.53–70.72; p = 0.017). Conclusions Sunitinib carries a relatively high incidence of hematologic toxicities and a substantial increased risk of high-grade neutropenia in patients with GIST. Appropriate prevention and management seem to be inevitable.