Navigating third-line therapies: A comprehensive review of regorafenib versus fruquintinib with placebo comparator for metastatic colorectal cancer—A systematic review and meta-analysis.

Abstract

e15514 Background: The choice of third-line and beyond therapies for metastatic colorectal cancer (mCRC) remains uncertain. Regorafenib and Fruquintinib have shown significant benefits compared to placebo, but no direct clinical comparison exists. This systematic review and network meta-analysis aimed to evaluate the efficacy and safety of these two agents in patients with refractory mCRC. Methods: A comprehensive search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) comparing Regorafenib or Fruquintinib to placebo in mCRC. Two reviewers independently extracted data and assessed study quality. Direct pairwise meta-analyses and indirect comparisons were performed using network meta-analysis to assess overall survival (OS), progression-free survival (PFS), and toxicity profiles. Data analysis was done using RevMen V.5.4.1 and forest plots were constructed. Results: Four RCTs involving 1,410 patients were included in the analysis. Both Regorafenib and Fruquintinib improved survival compared to placebo in direct comparisons. Indirectly, Fruquintinib showed no significant difference in OS compared to Regorafenib (HR 0.95; 95% CI 0.66–1.50). For PFS, Fruquintinib exhibited a trend toward superiority over Regorafenib (HR 0.62; 95% CI 0.41–1.12), though the result was not statistically significant. Regarding safety, Fruquintinib demonstrated significantly lower all-grade toxicity (OR 0.70; 95% CI 0.62–0.81), particularly for proteinuria (OR 0.28; 95% CI 0.10–0.84). No significant difference was observed for grade 3–5 toxicities (OR 0.89; 95% CI 0.61–1.35). Conclusions: Regorafenib and Fruquintinib offer similar clinical benefits in refractory mCRC, but Fruquintinib may have a more favorable toxicity profile, particularly for all-grade adverse events. These findings suggest that Fruquintinib could be a preferred option based on tolerability, though both agents remain essential therapeutic options in advanced mCRC.