Regorafenib (Stivarga)

FDA approved 9/27/2012.

General information

Class/mechanism: Small molecule inhibitor of multiple tyrosine kinases, such as: VEGFR1, VEGFR2, VEGFR3, KIT, RET, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl, which are involved in tumor cell proliferation, survival, and angiogenesis. Its major active metabolites are M-2 and M-5.
Route: PO
Extravasation: n/a
Black Box Warning: Severe and sometimes fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue regorafenib for hepatotoxicity as manifested by elevated liver function tests (LFTs) or hepatocellular necrosis, depending upon severity and persistence.

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the package insert.

Diseases for which it is used

• Colon cancer
• GIST (Gastrointestinal Stromal Tumor)
• Renal cancer

Clinical trials

• CORRECT: A randomized, double-blind, placebo-controlled phase III study of regorafenib plus BSC versus placebo plus BSC in patients with metastatic colorectal cancer (CRC) who have progressed after standard therapy 2012 ASCO Gastrointestinal Cancers Symposium abstract LBA385; Clinicaltrials.gov NCT01103323; Bayer study 14387
• Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor after Failure with Imatinib or Sunitinib; Clinicaltrials.gov NCT01068769
• List of regorafenib clinical trials at Cancer.gov

Patient drug information

• Regorafenib (Stivarga) package insert PDF pages 19-23
• Regorafenib (Stivarga) patient drug information (Chemocare)
• Regorafenib (Stivarga) patient drug information (UpToDate)

History of changes in FDA indication

• 9/27/2012: FDA approved for "patients with metastatic colorectal cancer (mCRC) 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."
• 2/25/2013: FDA approved for "patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease."

Also known as

BAY 73-4506.