FDA Approves Regorafenib for Metastatic CRC


Photo credit: Bayer Pharmaceuticals

The FDA today approved the use of the drug regorafenib (brand name Stivarga) for patients whose metastatic colorectal cancer has progressed despite all currently approved treatment regimens.

This is the second new drug approved by the FDA recently after a drought of 5 years in approving new treatments for metastatic colorectal cancer (mCRC). Regorafenib was placed into the  FDA’s “fast-track” approval process after the international, multicenter Phase III CORRECT trial  showed improved survival (from 5 to 6.4 months) in all mCRC patients, including those having both non-mutated and mutated KRAS types.

Regorafenib (Stivarga) is a biologic drug in pill form which has a broader target than other biologics used to treat mCRC patients. FDA approval opens the door for Medicare and other insurers to cover the cost of this drug in patients whose metastatic disease has progressed despite all other standard therapies. 

About 25% of colorectal cancers are already advanced (metastatic or stage IV) at diagnosis, and another 25% of CRC patients (mostly those with stage III and some stage II) will develop metastases with a recurrent cancer. A few mCRC patients may achieve long-term survival, primarily when they are diagnosed with very limited metastatic disease which can be surgically removed. For most patients, there is not cure for metastatic CRC, but the amount of time they survive can be lengthened when patients have more treatment options.

Regorafenib (Stivarga) is a drug in pill form that targets the VEGFR—a protein that stimulates growth of new blood vessels to nourish a tumor–and also RAF, a protein in the MAPK pathway that stimulates cell growth.

“Regorafenib is a multitargeted inhibitor of a number of pathways that drive cancer,” explained Dr. Richard Goldberg, member and former chair of NCI’s Colorectal Cancer Task Force who also serves on Fight Colorectal Cancer’s Medical Advisory Board. “It is the first in its class of drugs to show activity in people with advanced colorectal cancer. It provides an additional option for people with disease that has progressed through conventional chemotherapies and other targeted agents. Because patients whose tumors harbor Kras mutations have fewer treatment options due to resistance to the EGFR inhibitors cetuximab and panitumumab, this new agent should have particular utility for their treatment.”

From May 2010 to March 2011, the Phase III CORRECT trial enrolled 760 patients in cancer centers around the world whose metastatic disease had progressed either during or within 3 months after completing all standard treatments. Patients were randomly assigned to receive either regorafenib and “best supportive treatment,” or a placebo and best supportive treatment. Early results in the Phase III CORRECT clinical trial showed enough improvement in overall survival that placebo patients were offered the chance to switch to regorafenib, and the FDA put the drug on a fast-track for review.

The large trial showed improved survival time of 1.5 months (as well as improvement in other measures), with no difference between patients having either non-mutated and mutated KRAS genes. Some patients did show significantly more response to regorafenib than other people, so a next step will be to figure out which patients do best with this new drug.

Stivarga (regorafenib) carries a Boxed Warning alert about severe and fatal liver toxicity which occurred in some patient treated with Stivarga during the trial. The most frequent serious side effects include hand-foot skin reaction (17% of those who took the drug); fatigue (15%), diarrhea (8%) and high blood pressure and bilirubin blood levels (less than 10%). So as all second or third-line treatments for metastatic CRC, doctors and patients must consider the balance between possibly longer survival and the patient’s ability to tolerate side effects.

But FDA approval delivers one more weapon against metastatic CRC which progresses despite existing standard therapies. 

Sources:  FDA press release Sept. 27 2010; Journal of Clinical Oncology 30, 2012 (suppl 4; abstr LBA385)

For additional information:

(1)   If you have questions about regorafenib or the other newly FDA-approved aflibercept, call the Answer Line at 1-877-427-2111.

(2)   You can hear the experts discuss new CRC drugs in two Fight Colorectal Cancer archived webinars: A Peek at the Pipeline, April 18, 2012 with Dr. Rich Goldberg, an international expert in evaluating new treatment drugs; and What’s New in Colorectal Cancer Research? June 20, 2012 with Dr. Axel Grothey of the Mayo Clinic summarizing research reported at this year’s ASCO conference.

Disclosure: Fight Colorectal Cancer has accepted funding for projects and educational programs from sanofi-aventis and Bayer in the form of unrestricted educational grants. Fight Colorectal Cancer has ultimate authority over website content. See the Fight Colorectal Cancer Funding Policy and Disclosure.

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