Evaluation of progression-free survival by blinded independent central review in patients with progressive, well-differentiated pancreatic neuroendocrine tumors treated with sunitinib or placebo.

作者：Eric Van Cutsem, J. F. Seitz, Jean‐Luc Raoul, Juan W. Valle, Sandrine Faivre, Shem Patyna, Deno Klademenos, Dongxue Lu, Richard C. Chao, Éric Raymond · 发表于：Journal of Clinical Oncology · 年份：2011 · DOI：10.1200/jco.2011.29.4_suppl.249 · 被引用次数：6 · 研究领域：Neuroendocrine Tumor Research Advances、Neuroblastoma Research and Treatments、Pancreatic and Hepatic Oncology Research

249 Background: Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor with antiangiogenic activity. In a phase III, double-blind, placebo-controlled, randomized trial in patients with advanced, well-differentiated progressive pancreatic neuroendocrine tumors (NET), sunitinib 37.5 mg continuous daily dosing significantly improved investigator-assessed progression-free survival (PFS) compared with placebo (median, 11.4 months vs. 5.5 months; hazard ratio [HR] 0.418; 95% CI: 0.263, 0.662; P=0.0001). To evaluate the possibility that recognizable treatment- associated adverse events (AEs) might have impacted the efficacy results by unblinding the investigators, we conducted a retrospective blinded independent central review (BICR) of the tumor imaging scans. Methods: PFS was defined as the time from randomization to the first objective progression of disease or death due to any cause, whichever occurred first. Baseline and on-study CT/MRI scans were evaluated independently according to a two-reader, two-time point lock, followed by a sequential locked read, batch mode paradigm, by independent, third party radiologists. Reading radiologists were blinded to investigator tumor assessments and AEs; discrepancies were adjudicated by a similarly blinded and independent third radiologist. Results: Overall, 171 patients were randomized to treatment (sunitinib, n=86, placebo, n=85). Scans were collected retrospectively for 170 (99.4%) patients. Complete scan sets/time poin...