Everolimus for Advanced Pancreatic Neuroendocrine Tumors

摘要: A B S T R AC BACKGROUND Everolimus, an oral inhibitor of mammalian target rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, two phase 2 studies. We evaluated the agent a prospective, randomized, 3 study. METHODS randomly assigned 410 who had advanced, low-grade or intermediategrade tumors radiologic progression within previous 12 months to receive everolimus, at dose 10 mg once daily (207 patients), placebo (203 both conjunction best supportive care. The primary end point was progression-free survival intention-to-treat analysis. In case whom occurred during study, treatment assignments could be revealed, and been were offered open-label everolimus. Results median 11.0 everolimus as compared 4.6 (hazard ratio for disease death from any cause 0.35; 95% confidence interval [CI], 0.27 0.45; P<0.001), representing 65% reduction estimated risk death. Estimates proportion alive 18 34% (95% CI, 26 43) 9% 4 16) placebo. Drug-related adverse events mostly grade 1 included stomatitis (in 64% group vs. 17% group), rash (49% 10%), diarrhea (34% fatigue (31% 14%), infections (23% 6%), which primarily upper respiratory. Grade that more frequent than anemia (6% 0%) hyperglycemia (5% 2%). exposure longer by factor 2.3 (38 weeks 16 weeks). Conclusions placebo, significantly prolonged among progressive associated low rate severe events. (Funded Novartis Oncology; RADIANT-3 ClinicalTrials.gov number, NCT00510068.)