FDA Approves Regorafenib for Metastatic Colorectal Cancer

Regorafenib, an oral multikinase inhibitor, has been approved to treat metastatic colorectal cancer, the Food and Drug Administration announced on Sept. 27.

The approved indication is for the treatment of patients with metastatic colorectal cancer, "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."

Dr. Eric Van Cutsem

Approval was based on the results of one study of 760 patients with metastatic colorectal cancer, who had been treated previously. Among those randomized to treatment with regorafenib and best supportive care, median overall survival was 6.4 months, compared with a median of 5 months among those who received placebo and best supportive care. Median progression-free survival was 2 months among those on regorafenib, compared with 1.7 months among those on placebo, according to the FDA statement announcing the approval.

In June, CORRECT trial investigator Dr. Eric Van Cutsem of University Hospital Leuven in Gasthuisberg, Belgium, reported that regorafenib improved survival in patients with KRAS mutations as well as those with wild-type KRAS. "Regorafenib increases overall survival and progression-free survival in patients with metastatic colorectal cancer who have failed current standard therapies. The benefit is shown across prespecified subgroups," he said at the American Society of Clinical Oncology annual meeting.

Bayer HealthCare Pharmaceuticals will market the drug as Stivarga. The recommended dose is 160 mg, once daily for the first 21 days of each 28-day cycle.

Regorafenib "is the latest colorectal cancer treatment to demonstrate an ability to extend patients’ lives and is the second drug approved for patients with colorectal cancer in the past 2 months," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the statement.

In August, the FDA approved ziv-aflibercept (Zaltrap) for use in combination with a FOLFIRI (folinic acid, fluorouracil, and irinotecan) chemotherapy regimen for metastatic colorectal cancer. .

The most common adverse effects associated with regorafenib treatment included weakness or fatigue, loss of appetite, palmar-plantar erythrodysesthesia, diarrhea, mucositis, weight loss, infection, hypertension, and dysphonia, the FDA said.

In clinical trials, there were severe and fatal cases of hepatotoxicity associated with treatment, which will be highlighted in the boxed warning in the drug’s label, the FDA said.

Regorafenib was approved within 6 months of the company’s application for approval, under the FDA’s review program for drugs that provide a major advance in treatment or provide a treatment for a disease for which there is no adequate treatment.

Click here to view the drug’s label.