Efficacy and safety of fruquintinib combined with PD-1 inhibitors in the treatment of refractory metastatic colorectal cancer: a systematic review and meta-analysis

Fruquintinib, a VEGFR1–3 tyrosine kinase inhibitor, is approved for treating refractory metastatic colorectal cancer. Recent clinical practice has shown that combining fruquintinib with programmed cell death protein 1 (PD-1) inhibitors can achieve better efficacy.The objective of this study is to assess the efficacy and safety of combining PD-1inhibitors with fruquintinib. We systematically searched PubMed, Cochrane Library, Embase, Wanfang, and CNKI up to 28 August 2024 for studies comparing fruquintinib combined with PD-1 inhibitors to fruquintinib alone. RevMan software was used to perform meta-analyses of survival data for the included studies. A total of 9 retrospective cohort studies and 1 randomized controlled trial were included, involving a total of 716 patients. Compared with the monotherapy group, the combination therapy group had a greater Overall Response Rate [RR = 2.45,95% CI (1.83, 3.56), <i>p</i> &lt; 0.00001], Disease Control Rate [RR = 1.37,95% CI (1.64,4.79), <i>p</i> = 0.0002], and progression-free survival [HR = 0.64,95% CI (0.49, 0.84), <i>p</i> = 0.001]. However, there was no significant difference in overall survival between the two groups. The incidence of adverse effects was identical in both groups. Fruquintinib combined with PD-1 inhibitors was more effective than fruquintinib alone in the treatment of advanced colorectal cancer, with acceptable safety. PROSPERO (registration number CRD42024583116).