1 INDICATIONS AND USAGE
Stivarga® is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.
5 WARNINGS AND PRECAUTIONS
5.8 Wound Healing Complications
Since vascular endothelial growth factor receptor (VEGFR) inhibitors such as regorafenib can impair wound healing, treatment with regorafenib should be stopped at least 2 weeks prior to scheduled surgery.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of VEGFR1, VEGFR2, VEGFR3 at concentrations of regorafenib that have been achieved clinically.
- Metabolism: Regorafenib is metabolized by CYP3A4 and UGT1A9.
14 CLINICAL STUDIES
14.1 Colorectal Cancer
History of KRAS evaluation was reported for 729 (96%) patients; 430 (59%) of these patients were reported to have KRAS mutation.