Meta-analysis of randomized controlled trials (RCTs) to evaluate the incidence of hemorrhage and venous thromboembolism (VTE) events in patients with gastrointestinal (GI) cancers treated with fruquintinib.

118 Background: Fruquintinib is a novel cancer therapy that was recently approved by the US FDA as a third-line treatment for metastatic colorectal cancer (mCRC). It works by inhibiting the vascular endothelial growth factor receptors, that leads to blocking of angiogenesis which is essential for the tumor proliferation. Close monitoring is always crucial in order to promptly detect and manage any adverse events. This study aims to assess the risk of hemorrhagic and VTE events in patients with GI cancers treated with fruquintinib. Methods: A comprehensive literature search was conducted using MEDLINE, EMBASE, and COCHRANE databases from inception through August 12th, 2024. Phase II/III RCTs utilizing fruquintinib in GI cancers reporting hemorrhage or VTE events as an adverse event were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. Random effects model was applied. Results: A total of 1872 patients were included. Data were pooled from three phase III RCTs (FRESCO, FRESCO-2, FRUTIGA) and one phase II RCT, all reporting VTE events including deep vein thrombosis and pulmonary embolism and hemorrhage. FRESCO, FRESCO-2, and the phase II trials involved patients with mCRC, comparing fruquintinib to placebo. FRUTIGA trial incorporated patients with gastric or gastroesophageal junction adenocarcinoma, comparing fruquintinib + paclitaxel to placebo + paclitaxel. High-grade hemorrhage incidence was higher in the fruquintinib arm compared to the control arm (29.00% vs 21.18%, RR 1.62; 95% CI: 1.26-2.08, P=0.0001). In the mCRC subgroup, high-grade hemorrhage rate was also higher and statistically significant in the fruquintinib arm 20.87% vs 11.22% (RR 1.84; 95% CI: 1.25-2.70; P=0.002). Incidence of any grade or high grade VTE events was neither statistically significant in GI cancer population or mCRC subgroup. Incidence of any grade VTE events in GI cancer group and mCRC subgroup was 2.74% vs 2.15% (RR, 1.23; 95% CI: 0.53-2.88; P=0.63) and 2.68% vs 1.53% (RR, 0.95; 95% CI: 0.09-9.67; P=0.97), respectively. Rate of high grade VTE events in GI cancer cohort was 1.67% vs 0.67% (RR, 1.96; 95% CI: 0.52-7.36; P=0.32), while in mCRC subgroup was 1.79% vs 0.76% (RR, 1.08; 95% CI: 0.06-19.98; P=0.96). Conclusions: This meta-analysis demonstrates that patients with GI cancers, including mCRC, treated with fruquintinib have higher incidence of high-grade hemorrhage. These findings underscore the importance of individualized risk assessment, especially for patients predisposed to hemorrhagic complications. No increased risk of VTE events was noted in patients treated with fruquintinib compared to placebo.