Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors

作者：Éric Raymond, Laëtitia Dahan, Jean‐Luc Raoul, Yung‐Jue Bang, Ivan Borbath, Catherine Lombard‐Bohas, Juan W. Valle, Peter P. Metrakos, Denis Michel Smith, Aaron I. Vinik, Jen‐Shi Chen, Dieter Hörsch, Pascal R. Hammel, Bertram Wiedenmann, Eric Van Cutsem, Shem J. Patyna, Dongrui Ray Lu, C. Blanckmeister, Richard C. Chao, Philippe B Ruszniewski · 发表于：New England Journal of Medicine · 年份：2011 · DOI：10.1056/nejmoa1003825 · 被引用次数：2568 · 研究领域：Neuroendocrine Tumor Research Advances、Pancreatic and Hepatic Oncology Research、Lung Cancer Research Studies

BACKGROUND: The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials. METHODS: We conducted a multinational, randomized, double-blind, placebo-controlled phase 3 trial of sunitinib in patients with advanced, well-differentiated pancreatic neuroendocrine tumors. All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline. A total of 171 patients were randomly assigned (in a 1:1 ratio) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo. The primary end point was progression-free survival; secondary end points included the objective response rate, overall survival, and safety. RESULTS: The study was discontinued early, after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib. Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group (hazard ratio for progression or death, 0.42; 95% confidence interval [CI], 0.26 to 0.66; P<0.001). A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied. The objective response rate was 9.3% in the sunitinib group versus 0% in the placebo g...