Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study

摘要: Summary Background Adrenocortical carcinoma is a rare, aggressive cancer for which few treatment options are available. Linsitinib (OSI-906) potent, oral small molecule inhibitor of both IGF-1R and the insulin receptor, has shown acceptable tolerability preliminary evidence anti-tumour activity. We assessed linsitinib against placebo to investigate efficacy in patients with advanced adrenocortical carcinoma. Methods In this international, double-blind, placebo-controlled phase 3 study, adult histologically confirmed locally or metastatic were recruited at clinical sites nine countries. Patients randomly assigned (2:1) twice-daily 150 mg via web-based, centralised randomisation system stratified according previous systemic cytotoxic chemotherapy carcinoma, Eastern Cooperative Oncology Group performance status, use one more antihyperglycaemic therapy randomisation. Allocation was concealed by blinded block size permuted The primary endpoint overall survival, calculated from date until death any cause. analysis done intention-to-treat population. This study registered ClinicalTrials.gov, number NCT00924989. Findings Between Dec 2, 2009, July 11, 2011, 139 enrolled, whom 90 49 placebo. trial unblinded on March 19, 2012, based data monitoring committee recommendation due failure increase either progression-free survival survival. At database lock 92 deaths, no difference noted between (median 323 days [95% CI 256–507] vs 356 [249–556]; hazard ratio 0·94 0·61–1·44]; p=0·77). most common treatment-related adverse events grade worse group fatigue (three [3%] group), nausea (two [2%] none), hyperglycaemia none). No deemed be related; (due sepsis megacolon) related. Interpretation did not so cannot recommended as general patient Further studies receptor inhibitors, together genetic profiling responders, might pave way toward individualised improved therapeutic Funding Astellas.