Stivarga (Regorafenib)

Regorafenib, manufactured by Bayer,  is the third drug FDA-approved for treatment of GIST. The FDA approved regorafenib for GIST resistant to imatinib and sunitinib in February 2013, and it is also approved for GIST in Canada, Chile, Ecuador, Japan, Uruguay, and Venezuela. An application for European approval is pending.  Patients in countries where regulatory approval has not yet been obtained may be able to access regorafenib through clinical trial NCT01689376 by contacting Bayer at this email address:

Regorafenib, brand name Stivarga and formerly known as BAY 73-4506 and as fluoro-sorafenib, was developed by Bayer. Regorafenib inhibits both proliferation-related and angiogenesis-related targets, threby inhibiting tumor growth and blood supply. Regorafenib is structurally similar to sorafenib, with a change in a single atom that gives it an additional mechanism of action: a second blockade of angiogenesis via inhibition of Tie-2. For an image showing how regorafenib is related to sorafenib, see this link.

Here are details from the 2/25/2013 FDA press release:

FDA stated “The U.S. Food and Drug Administration today expanded the approved use of Stivarga (regorafenib) to treat patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease….. With this new approval, Stivarga is intended to be used in patients whose GIST cancer cannot be removed by surgery or has spread to other parts of the body (metastatic) and is no longer responding to Gleevec (imatinib) and Sutent (sunitinib), two other FDA-approved drugs to treat GIST…… Stivarga was reviewed under the FDA’s priority review program, which provides an expedited six-month review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. The drug was also granted orphan product designation because it is intended to treat a rare disease.”


How does regorafenib (Stivarga) work?

Regorafenib inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, KIT, PDGFR and Raf kinases, plus the angiogenesis-related Tie2 kinase.

Definition from NCI Drug Dictionary: An orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Multikinase inhibitor BAY 73-4506 binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling.

How should I take my regorafenib (Stivarga)?

Regorafenib is to be taken in the morning with a low-fat breakfast (about 8 grams of fat). Consuming a high-fat meal with regorafenib decreases its bioavailability.


What is the typical dose and schedule for regorafenib(Stivarga)?

The indicated dose is 160 mg per day, which is achieved  with four 40-mg pills.  A treatment cycle includes three weeks of daily drug followed by one week without drug (washout).  In the trials of regorafenib for GIST, many patients required a dose reduction.  Therefore, your physician will determine the best dose for you once you have begun therapy, depending on whether you develop side effects.


What drug interactions occur with regorafenib (Stivarga)?

Regorafenib is metabolized by the liver enzyme CYP3A4; therefore foods, herbs, and drugs that change the levels of this enzyme will affect regorafenib absorption.

Avoid substances that induce (increase) CYP3A4 because these would decrease your effective dose of regorafenib:

  • St. John’s wort
  • rifampin
  • phenytoin
  • carbamazepine
  • phenobarbitol

Avoid substances that inhibit (decrease) CYP3A4 because these would increase your effective dose of regorafenib:

  • grapefruit juice
  • clarithromycin
  • itraconazole
  • ketoconazole
  • nefazadone
  • posaconazole
  • telithromycin
  • voriconazole


Where can I see more information about taking regorafenib (Stivarga) for GIST?

Bayer’s Stivarga patient website is at
This website provides details about how to take regorafenib, managing side effects, and access to a patient education materials, as well as other resources. LINK HERE to download Bayer’s patient education booklet about Stivarga.


Can I get financial assistance for my regorafenib (Stivarga) prescription?

Bayer’s REACH program at 1-866-639-2827 provides oncology nurses who can discuss patient concerns and assist with pharmacies and financial issues to gain access to regorafenib (Stivarga).