FDA Approves Sunitinib for Pancreatic Neuroendocrine Tumors

Roxanne Nelson

May 20, 2011

May 20, 2011 — The US Food and Drug Administration (FDA) has approved sunitinib malate (Sutent, Pfizer, Merck) for the treatment of pancreatic neuroendocrine tumors (NETs), making it the first antivascular endothelial growth factor receptor (anti-VEGF) therapy for this disease.

Sunitinib, a tyrosine kinase inhibitor, was approved for the treatment of progressive, well-differentiated NETs in patients with unresectable locally advanced or metastatic disease. Pancreatic NET is a rare cancer that occurs in an estimated 2 to 4 people per million annually worldwide, and fewer than 1000 new cases are reported in the United States each year.

Less than a month ago, the FDA approved everolimus (Afinitor, Novartis) to treat this disease. Before these 2 new approvals, there had been no new drugs for this disease in the United States for nearly 30 years.

"FDA believes it is important to provide cancer patients with as many treatment options as possible," said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, in a statement. "The agency is committed to working with companies to bring innovative new therapies to the market and encourages companies to continue exploring additional uses for approved products."

The FDA approval is based on data from the SUN 1111, a pivotal phase 3 trial showing that sunitinib provided a significant improvement in progression-free survival compared with placebo (10.2 vs 5.4 months; P = .000146). As previously reported by Medscape Medical News, the objective response rate was 9.3% in the sunitinib group and 0% in the placebo group.

In addition, the probability of progression-free survival at 6 months was 71.3% in the sunitinib group and 43.2% in the placebo group. Although overall survival data were not mature at the time of final analysis, 9 patients receiving sunitinib died compared with 21 patients in the placebo group.

In February 2009, the independent data monitoring committee recommended that randomization to the study be halted early in the interest of patient safety because of the risk for serious adverse events, disease progression, and death among patients in the placebo group.

The decision to halt the trial was also based on the very strong likelihood that the study would meet its primary endpoint if it continued to completion, but according to Pfizer, this may have led to an overestimate of the magnitude of the progression-free survival effect.

The most common adverse events associated with sunitinib were diarrhea, nausea, asthenia, vomiting, and fatigue. Each was observed in 30% or more of the patients. The most common grade 3 or 4 adverse events in patients who received sunitinib were neutropenia (12%) and hypertension (10%).

"This approval is welcome news for physicians who have struggled to find a treatment option that shows a substantial clinical benefit in treating advanced pancreatic NET," said lead investigator Eric Raymond, MD, professor of medical oncology and head of University Department of Medical Oncology Bichat-Beaujon, Clichy, France. "Pancreatic NET is a highly vascular tumor, and as the first anti-VEGF therapy approved for this disease, Sutent represents a treatment that attacks a key component of tumor growth."

Sunitinib has already received approval for the treatment of advanced pancreatic NET in Europe and 9 additional countries. It is also approved for both gastrointestinal stromal tumors after disease progression with and intolerance to imatinib mesylate and for advanced renal cell carcinoma in over 100 countries.

More information is available on the FDA Web site.


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