The tyrosine kinase inhibitor (TKI) sunitinib has been associated with a higher risk of hematologic toxicities such as anemia, thrombocytopenia, and high-grade neutropenia, in patients with gastrointestinal stromal tumors (GIST), according to a meta-analysis recently published in the International Journal of Colorectal Disease.

Sunitinib is a multiple-target TKI and a popular treatment option for patients with imatinib-resistant inoperable GIST. Evidence shows that its use can lead to longer progression-free survival in patients with drug-resistant GIST.

However, TKIs have been associated with frequent adverse effects, which often lead to treatment termination. Hematologic adverse reactions appear to be particularly frequent in patients receiving sunitinib; nonetheless, the reported incidence of these complications tends to vary greatly among studies.


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To assess the true incidence of hematologic toxicities associated with sunitinib, the authors conducted an extensive literature review in renowned medical databases using keywords such as sunitinib and gastrointestinal stromal tumors. After applying exclusion criteria, 13 trials, including more than 2500 patients in total, were selected for final review.

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Both the number of patients with hematologic adverse reactions and the total number of participants were extracted from each study in order to calculate incidence. All of the selected studies had a control arm to calculate confidence intervals (CI) and relative risk (RR).

The results showed a high incidence of hematologic toxicities. The most frequent adverse reaction was neutropenia with a pooled incidence of 41%, followed by thrombocytopenia with 31% and anemia with 26%. The incidence of high-grade cytopenia maintained the same trend, with a 9% incidence of severe neutropenia, compared to a 4% and 5% incidence of high-grade anemia and thrombocytopenia, respectively.

“In conclusion, all three hematologic toxicities of interest related to sunitinib are an issue for patients with GIST with relatively high combined incidences in this meta-analysis,” the authors wrote.

Due to the scarce data regarding anemia, RR was only calculated for high-grade thrombocytopenia and neutropenia. The RR for high-grade neutropenia was higher than 10, suggesting an increased risk of neutropenia in the population receiving sunitinib. On the other hand, a RR of roughly 4 showed no significant risk of high-grade thrombocytopenia.

“With respect to the results of this meta-analysis, routine monitoring of hematologic parameters in patients with GIST receiving sunitinib seems unavoidable,” the authors concluded.

Reference

Jiang X, Xiong F, Fu Q, et al. Hematologic toxicities of sunitinib in patients with gastrointestinal stromal tumors: a systematic review and meta-analysis. Int J Colorectal Dis. Published online July 22, 2022. doi:10.1007/s00384-022-04214-7