**2.4 Regorafenib combined with other anticancer agents**

In a phase I study, regorafenib combined with an anti-VEGF inhibitor, cetuximab, provided a clinical benefit, defined as the presence of stable disease or partial response. However, these promising preliminary findings need to be verified in future studies [17].

Combination therapy with regorafenib and FOLFIRI produced highly promising results, with overall disease control rate (DCR), median PFS, and median OS equal to 58.5%, 6.0 and 12.0 months, respectively [8]. An objective response rate to regorafenib combined with modified FOLFOX (mFOLFOX6) as the first-line treatment was no better than that observed in historical controls, with 85.4% DCR and median PFS of 8.5 months [18]. Negative results, specifically the lack of either OS or PFS benefit, were obtained in a study investigating the efficacy and toxicity of regorafenib plus ruxolitinib, a Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway [19].
