FDA approves Sutent for advanced pancreatic neuroendocrine tumors

FDA has approved sunitinib malate (Sutent, Pfizer) as the first anti-vascular endothelial growth factor (VEGF) therapy to treat progressive, well-differentiated pancreatic neuroendocrine tumors (NET) in patients with unresectable locally advanced or metastatic disease. Pancreatic NET is a rare cancer reported in 2 to 4 people per million annually worldwide.

Sutent is an oral multikinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation, and spread of cancer. Two important Sutent targets, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) are expressed by many types of solid tumors and are thought to play a crucial role in angiogenesis, the process by which tumors acquire blood vessels, oxygen, and nutrients needed for growth. Sutent also inhibits other targets important to tumor growth, including KIT, FLT3 and RET.

This is the second new approval by FDA to treat patients with this disease; on May 5, the agency approved everolimus (Afinitor, Novartis). The 2 approvals are said to mark the first new treatments in about 30 years for advanced pancreatic neuroendocrine tumors.

“Pancreatic NET is a disease for which there has been no new therapies introduced in many years,” said Azah Borham, PharmD, director, US regional outcomes research at Pfizer, told Formulary. “Although pancreatic NET is often considered an indolent disease, patients do progress to the metastatic state.”

Once a patient’s disease has metastasized and is no longer resectable, the median survival for these patients is 1.8 years (range 1.4–2.7), and the 5-year survival rate is 16%, which represents a need for novel treatment options, according to Dr Borham.

“The age-adjusted incidence of pancreatic NETs has been reported to be as low as 0.32 cases per 100,000 in the United States,” Beata Korytowsky, associate director, global outcomes research, Pfizer.

“However, a slightly higher incidence has been reported in autopsy studies, suggesting pancreatic NETs frequently go unnoticed because often these tumors are asymptomatic. Due to the infrequent occurrence, the budget impact is expected to be nominal,” Korytowsky said. “In addition, according to previously reported investigator-assessed data, patients have the potential to experience an almost 6-month benefit in progression-free survival [PFS], which represents an almost doubling of PFS over placebo. Thus, the availability of a treatment that prolongs survival in patients with advanced disease will fulfill a significant unmet need.”

FDA approval is based on data from the SUN 1111 trial, a multicenter, international, randomized, double-blind, placebo-controlled phase 3 study (n=171) that demonstrated Sutent provided a clinically significant improvement in progression-free survival (PFS) compared to placebo (10.2 vs 5.4 months, P=.000146) in this patient population. Treatment with Sutent also yielded a statistically significant improvement in tumor response, with an objective response rate (ORR) of 9.3% (95% CI: 3.2, 15.4, P=.0066). No objective responses were observed with placebo. In addition, while overall survival (OS) was not mature at the time of final analysis, 9 deaths were observed in patients enrolled in the SUTENT arm versus 21 deaths in patients enrolled in the placebo arm.

In patients treated with Sutent for neuroendocrine pancreatic tumors, the most commonly reported side effects included diarrhea, nausea, vomiting, fatigue, anorexia, high blood pressure, asthenia, abdominal pain, changes in hair color, stomatitis, and a decrease in infection-fighting white blood cells.

Sutent has been approved for advanced pancreatic NET in Europe and 9 additional countries. Sutent is also approved for both gastrointestinal stromal tumors after disease progression on or intolerance to imatinib mesylate, and advanced renal cell carcinoma in more than 100 countries and has been studied in more than 10,000 patients in clinical trials. To date, with more than 5 years of experience, more than 100,000 patients have been treated with Sutent worldwide.