Sunitinib, approved to treat renal cell carcinoma and gastrointestinal stromal tumors, boosts survival rates in patients with neuroendocrine pancreatic tumors.
ORLANDO, FL—Pancreatic neuroendocrine tumors are rare, reported in 2 to 4 people per million annually worldwide. Current treatment options are limited, but the final results of an international, Phase 3 trial presented at the 2010 Gastrointestinal Cancers Symposium indicate that sunitinib (Sutent), which is currently approved to treat renal cell carcinoma and as a second-line treatment for gastrointestinal stromal tumors, found the drug to more than double progression-free survival in patients with neuroendocrine pancreatic tumors.
Between June 2007 and April 2009, the trial randomized 171 patients (median age, 56 years) with progressive, well-differentiated, malignant pancreatic neuroendocrine tumors to either sunitinib 37.5 mg/day (n = 86) plus best supportive care or to placebo plus best supportive care (n = 85). The primary endpoint was progression-free survival (PFS) with a target enrollment of 340 patients; however, the study was stopped early per the recommendation of an independent Data Monitoring Committee because sunitinib showed significant benefit and the study’s primary endpoint had been met.
Patients in the sunitinib arm had experienced a median PFS of 11.4 months compared with 5.5 months for patients in the placebo arm (hazard ratio [HR], 0.418; < .001). The objective response rate with sunitinib was 9.3% (2 complete and 6 partial responses; 95% confidence interval, 3.2%-15.4%). Patients in the sunitinib arm also had prolonged overall survival (HR, 0.409; = .0204), which was a secondary endpoint. There were 9 deaths in the sunitinib arm compared with 21 in the placebo arm, but median overall survival was not reached in either arm (HR, 0.404; = .0186).
"The magnitude of Sutent’s benefit in the pancreatic neuroendocrine tumor patient population was an encouraging finding," said Eric Raymond, MD, PhD, professor of medical oncology and head of University Department of Medical Oncology (Service Inter Hospitalier de Cancerologie) Bichat-Beaujon, Clichy, France, and lead investigator of the study. "These findings offer hope to a patient population for whom there are limited treatment options," he added.
Sunitinib displayed an acceptable safety profile in patients with advanced neuroendocrine pancreatic tumors, and adverse events observed in these patients were similar to those observed in other sunitinib studies. The most commonly reported grade 3-4 adverse events were neutropenia (12%), hypertension (9.6%), hand-foot syndrome (6%), leukopenia (6%) abdominal pain (4.8%), diarrhea (4.8%), asthenia (4.8%), fatigue (4.8%), and hypoglycemia (4.8%). Grade 5 cardiac failure was experienced by 1.2% of the patients receiving sunitinib.
In a statement issued to the press, Mace Rothenberg, MD, senior vice president of clinical development and medical affairs for Pfizer’s Oncology Business Unit, noted "This trial advances our understanding of the use of novel targeted therapies in a patient population with limited treatment options." He added, "We are pleased to be working toward filling an unmet patient need, as we did with Sutent 4 years ago in patients with kidney cancer and gastrointestinal stromal tumors."
Based on the findings of this study, Pfizer has filed supplemental applications for Sutent in the treatment of pancreatic neuroendocrine tumors with the regulatory authorities in the United States, Europe, and Canada.
2010 GI Symposium Abstract 127