Direct and indirect comparison of progression-free survival (PFS) for patients with refractory mCRC treated with regorafenib, fruquintinib, and TAS-102 all showed benefit when compared with placebo. For PFS, the hazard ratio (HR) for fruquintinib was 0.26 (95% CI, 0.17–0.41), the HR for regorafenib was 0.41 (95% CI, 0.30–0.57), and the HR for TAS-102 was 0.46 (95% CI, 0.34–0.61). Also, fruquintinib showed significant superiority when compared with TAS-102 (HR 0.57; 95% CI, 0.34–0.95). No significant difference was found in the indirect comparison between fruquintinib and regorafenib (HR 1.58; 95% CI, 0.93–2.71), or indirect comparison between regorafenib and TAS-102 (HR 0.90; 95% CI, 0.59–1.39). The results of the comparative data for PFS between regorafenib, fruquintinib, and TAS-102 are shown in Figure 6.