Regorafenib, a new, targeted, oral drug, demonstrated the ability to control metastatic gastrointestinal stromal tumor (GIST), which is an uncommon and life-threatening form of sarcoma, after the disease had become resistant to all existing therapies. Regorafenib was able to control GIST nearly 4 months longer than placebo in patients for whom imatinib and sunitinib were no longer effective.

GIST is a rare form of sarcoma that develops in the gastrointestinal tract, mainly in the stomach and small intestine. GIST is estimated to affect more than 5,000 people per year in the United States and about 8,000 in Europe. The treatment of GIST, even in its advanced metastatic stage, has been dramatically improved with two oral targeted drugs, imatinib and sunitinib. To date, these are the only two FDA-approved treatments with the proven ability to control GIST. However, in more than 85% of patients, GIST becomes resistant to these drugs after 7 years and the disease worsens with fatal results.

Regorafenib is a novel rationally designed drug manufactured by Bayer HealthCare Pharmaceuticals that was FDA-approved in September 2012 to treat metastatic colon cancer after failure of standard chemotherapy. It blocks several cancer-promoting enzymes called kinases, which spur runaway growth in GIST and other cancers.

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This phase III international trial involved 199 treatment-resistant GIST patients at 57 hospitals in 176 countries. Of the 199 patients, 133 received a regorafenib pill daily for 3 weeks followed by a 1-week break, while 66 received a matching placebo. The patients were monitored for at least 1 year after the trial began.  The study’s “cross-over” design made it possible to treat those patients whose tumors grew, and 85% of the patients initially on placebo were able to receive regorafenib, which then controlled the disease in these patients as well.

“When added to best supportive care, regorafenib significantly improves disease control, as measured by progression-free survival time in patients with GIST after progression which represents failure of all other therapies,” said George Demetri, MD, of Dana-Farber, principal investigator of this clinical trial.

As for other targeted therapies, the drug did not often shrink tumors but controlled the disease for an average of 4.8 months before it progressed, while patients in the placebo group experienced less than 1 month (0.9 month) before the disease worsened.

Adverse events occurred at a high rate, and they included high blood pressure; fatigue; diarrhea; and redness, swelling, numbness and peeling of skin on the hands and feet. These side effects were managed by reducing or interrupting the regorafenib treatment, the report said.

This study was published in the Lancet (2012; doi:10.1016/S0140-6736(12)61857-1).