The FDA has approved Sutent (sunitinib) for the treatment of patients with unresectable, locally advanced, or metastatic pancreatic neuroendocrine tumors (pNET). Sunitinib joins everolimus (Afinitor), which the FDA approved for pNET earlier this month, as the first new treatments for the rare disease in nearly 30 years.

Last month, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 8-2 in support of the pNET indication for sunitinib, an oral tyrosine kinase inhibitor that blocks the vascular endothelial growth factor pathway. ODAC’s recommendation was based on data from the SUN 1111 pivotal phase III trial, which randomized 171 patients with pNET to either 37.5 mg daily of sunitinib or placebo.

The FDA reported that median progression-free survival (PFS) in the sunitinib cohort was 10.2 months versus 5.4 months in the placebo group. Sunitinib also demonstrated anti-tumor activity, with an objective response rate of 9.3% versus no response in the placebo arm.

The most frequently occurring side effects in the sunitinib population were diarrhea, nausea, vomiting, fatigue, anorexia, high blood pressure, energy loss (asthenia), stomach (abdominal) pain, changes in hair color, inflammation of the mouth (stomatitis), and a decrease in infection-fighting white blood cells (neutropenia).

An independent data and safety monitoring committee halted the trial before completion due to the greater survival benefit and fewer deaths and adverse events observed in the sunitinib cohort. Twenty-one deaths occurred in the placebo group versus 9 deaths among patients treated with sunitinib.

Given the PFS and toxicity results, “It was considered very inappropriate to continue randomizing patients [and] taking the risk of having patients entering into the trial being treated with placebo with [the associated] higher risk of death and…higher risk of adverse events,” said Eric Raymond, MD, principal investigator of the SUN 1111 phase III trial, and professor of medical oncology and head of the University Department of Medical Oncology (Service Inter Hospitalier de Cancerologie) Bichat-Beaujon, Clichy, France. “It’s very rare to have to stop a trial for [the] positivity [of its results],” Raymond added.

When the ODAC panel met in April, the committee discussed whether the early SUN 1111 discontinuation might have actually led to the overestimation of sunitinib’s benefit in patients with pNET. However, the majority of panel members concluded the PFS data were sufficient, especially given the limited treatments available for the rare pancreatic cancer.

According to the manufacturer, Pfizer Inc, sunitinib is already approved for a pNET indication in Europe and 9 other countries. Sunitinib has previously been approved by the FDA to treat patients with gastrointestinal stromal tumors and metastatic renal cell carcinoma.