Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management

Regorafenib is a broad-spectrum oral multikinase inhibitor that targets several angiogenic, oncogenic, and stromal receptor tyrosine kinases that support the tumor microenvironment. Results from the pivotal Phase III Patients with Metastatic Colorectal Cancer Treated with Regorafenib or Placebo After Failure of Standard Therapy (CORRECT) trial showed that the addition of regorafenib to best supportive care resulted in a significant improvement in median overall survival and progression-free survival compared with placebo plus best supportive care in patients with metastatic colorectal cancer (mCRC) following all available approved therapies. Thus, regorafenib is the first oral multikinase inhibitor indicated for mCRC; it currently has approval in the USA, EU, Japan, Canada, and Singapore for the treatment of mCRC patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy, and, if the tumor is KRAS wild-type, an anti-epidermal growth factor receptor therapy. In this review, we highlight regorafenib's mechanism of action, present key efficacy data from the CORRECT trial, and discuss how to proactively manage common adverse events (eg, hand-foot skin reaction, hypertension, oral mucositis, diarrhea, and fatigue) experienced by patients receiving regorafenib. Increased awareness of potential adverse events associated with regorafenib and the implementation of proactive strategies to prevent, monitor, and manage these events early in the course of treatment will be instrumental in ensuring optimal patient management and continuation of regorafenib therapy.