Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review

Abstract

Objective: The efficacy and safety of regorafenib and fruquintinib are studied extensively in different populations and trials across the world to determine their potential benefits. Here we review the efficacy and safety of regorafenib and fruquintinib as third-line treatment option for colorectal cancer (CRC).

Background: CRC is the third most prevalent cancer worldwide, but the optimal third-line treatment option is still debatable. Regorafenib is a multikinase inhibitor that inhibits several cell signaling receptors, including vascular endothelial growth factor receptors (-1, -2, and -3) (VEGFRs), platelet-derived growth factor (PDGF), fibroblast growth factor, epidermal growth factor (EGF), angiotensin II, and Rapidly Accelerated Fibrosarcoma kinase pathway. On the other hand, fruquintinib inhibits signaling through the VEGFRs family. Regorafenib and fruquintinib have both received United States Food and Drug Administration (USFDA) approval for treating metastatic CRC (mCRC) in patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti- vascular endothelial growth factor therapy, and Rat sarcoma wild type, an anti- EGF receptor therapy.

Methods: A review of literature was conducted in PubMed and Embase with the keywords "regorafenib" OR "fruquintinib" AND "colorectal cancer" for clinical studies performed in randomized controlled settings and real-world settings.

Conclusions: Regorafenib and fruquintinib are effective and well tolerated options for the third-line treatment of patients with CRC. Both have a similar survival outcome with Regorafenib showing a slightly better toxicity profile.

Keywords: Metastatic colorectal cancer (mCRC); clinical trials; fruquintinib; regorafenib.

Figure 1

Mechanism of action for regorafenib and fruquintinib.