Regorafenib (Stivarga)

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.^[1]^[2]^[3]
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.^[1]

Diseases for which it is established (work in progress)

Diseases for which it is used

Patient drug information

History of changes in FDA indication

Colorectal cancer

2012-09-27: 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. (Based on CORRECT)

Gastrointestinal stromal tumor

2013-02-25: 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. (Based on GRID)

Hepatocellular carcinoma

2017-04-27: Approved for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. (Based on RESORCE)

History of changes in EMA indication

2013-08-26: Initial marketing authorization as Stivarga.

History of changes in Health Canada indication

2013-03-11: Initial notice of compliance for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-vascular endothelial growth factor (anti-VEGF) therapy, and, if KRAS wild type, an anti-epidermal growth factor receptor (anti-EGFR) therapy.
2013-10-14: New indication for adult patients with metastatic and/or unresectable GIST who have had disease progression on or intolerance to imatinib mesylate and sunitinib malate treatment.
2017-08-29: Indication revised for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-vascular endothelial growth factor (anti-VEGF) therapy, and, if RAS wild type, an anti-epidermal growth factor receptor (anti-EGFR) therapy.
2017-09-18: New indication for use in the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with one systemic therapy.

History of changes in PMDA indication

2013-03-25: Initial approval for the treatment of unresectable advanced or recurrent colorectal cancer.
2013-08-20: New additional indication for the treatment of gastrointestinal stromal tumor which has progressed after cancer chemotherapy.
2017-06-26: New additional indication for the treatment of unresectable hepatocellular carcinoma which has progressed after cancer chemotherapy.

Also known as

Code name: BAY 73-4506
Brand names: Nublexa, Regonix, Renib, Resihance, Stivarga

References

[insert-1] 1.0 ^1.1 ^1.2 Regorafenib (Stivarga) package insert

[2] Regorafenib (Stivarga) package insert (locally hosted backup)

[3] Stivarga manufacturer's website

[4] Regorafenib (Stivarga) patient drug information (Chemocare)

[5] Regorafenib (Stivarga) patient drug information (UpToDate)

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