PMID- 26802147 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20220321 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 27 IP - 4 DP - 2016 Apr TI - A randomized, double-blind, placebo-controlled phase II study to assess the efficacy and safety of mapatumumab with sorafenib in patients with advanced hepatocellular carcinoma. PG - 680-7 LID - 10.1093/annonc/mdw004 [doi] AB - BACKGROUND: This randomized, double-blind, placebo-controlled, phase II study evaluated the efficacy and safety of mapatumumab (a human agonistic monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 1) in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with advanced HCC (stratified by Barcelona Clinic Liver Cancer stage and Eastern Cooperative Oncology Group performance status) were randomized 1:1 to receive sorafenib (400 mg, twice daily per 21-day cycle) and either placebo (placebo-sorafenib arm) or mapatumumab (30 mg/kg on day 1 per 21-day cycle; mapatumumab-sorafenib arm). The primary end point was time to (radiologic) progression (TTP), assessed by blinded independent central review. Key secondary end points included progression-free survival, overall survival, and objective response. RESULTS: In total, 101 patients were randomized (placebo-sorafenib arm: N = 51; mapatumumab-sorafenib arm: N = 50). There was no significant difference in median TTP between both arms [5.6 versus 4.1 months, respectively; adjusted hazard ratio (one-sided 90% confidence interval) 1.192 (0-1.737)]. No mapatumumab-related benefit was identified when TTP was evaluated in the stratified subgroups. The addition of mapatumumab to sorafenib did not demonstrate improvement in the secondary efficacy end points. The reported frequency of adverse events (AEs) and serious AEs was comparable in both treatment arms. CONCLUSIONS: The addition of mapatumumab to sorafenib did not improve TTP or other efficacy end points, nor did it substantially change the toxicity profile of sorafenib in patients with advanced HCC. Based on these results, further development of the combination of mapatumumab and sorafenib in HCC is not planned. CI - (c) The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Ciuleanu, T AU - Ciuleanu T AD - Department of Medical Oncology, Prof. Dr Ion Chiricuta Institute of Oncology and UMF Iuliu Hatieganu, Cluj Napoca, Romania tudor@iocn.ro. FAU - Bazin, I AU - Bazin I AD - Federal State Budgetary Institution, Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of Medical Sciences, Moscow, Russia. FAU - Lungulescu, D AU - Lungulescu D AD - SC Oncolab SRL, Dolj County. FAU - Miron, L AU - Miron L AD - Iasi Regional Institute for Oncology, Iasi County, Romania. FAU - Bondarenko, I AU - Bondarenko I AD - Department of Oncology and Medical Radiology, Dnipropetrovsk Medical Academy, City Multispeciality Clinical Hospital # 4, Dnipropetrovsk, Ukraine. FAU - Deptala, A AU - Deptala A AD - Department of Oncology and Hematology, CSK MSW, Warsaw Department of Cancer Prevention, WNOZ WUM, Warsaw, Poland. FAU - Rodriguez-Torres, M AU - Rodriguez-Torres M AD - Fundacion de Investigacion, San Juan, Puerto Rico. FAU - Giantonio, B AU - Giantonio B AD - Department of Hematology-Oncology, Abramson Cancer Center of the University of Pennsylvania, Philadelphia. FAU - Fox, N L AU - Fox NL AD - Clinical Development, Human Genome Sciences, Inc., Rockville. FAU - Wissel, P AU - Wissel P AD - Clinical Development, GlaxoSmithKline, Upper Providence, USA. FAU - Egger, J AU - Egger J AD - Clinical Development, GlaxoSmithKline, Stockley Park, UK. FAU - Ding, M AU - Ding M AD - Statistics, GlaxoSmithKline, Upper Providence. FAU - Kalyani, R N AU - Kalyani RN AD - Clinical Development, Human Genome Sciences, Inc., Rockville. FAU - Humphreys, R AU - Humphreys R AD - Oncology Research. FAU - Gribbin, M AU - Gribbin M AD - Statistics, Human Genome Sciences, Inc., Rockville, USA. FAU - Sun, W AU - Sun W AD - Department of Hematology-Oncology, Abramson Cancer Center of the University of Pennsylvania, Philadelphia. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20160122 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Phenylurea Compounds) RN - 0 (Protein Kinase Inhibitors) RN - 25X51I8RD4 (Niacinamide) RN - 9ZOQ3TZI87 (Sorafenib) RN - WZ1025JPGR (mapatumumab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*administration & dosage MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage MH - Carcinoma, Hepatocellular/*drug therapy/pathology MH - Disease-Free Survival MH - Double-Blind Method MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Liver Neoplasms/*drug therapy/pathology MH - Male MH - Middle Aged MH - Niacinamide/administration & dosage/*analogs & derivatives MH - Phenylurea Compounds/*administration & dosage MH - Protein Kinase Inhibitors/administration & dosage MH - Sorafenib MH - Treatment Outcome OTO - NOTNLM OT - hepatocellular carcinoma OT - mapatumumab OT - progression-free survival OT - sorafenib EDAT- 2016/01/24 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/01/24 06:00 PHST- 2015/06/29 00:00 [received] PHST- 2016/01/07 00:00 [accepted] PHST- 2016/01/24 06:00 [entrez] PHST- 2016/01/24 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - S0923-7534(19)35755-2 [pii] AID - 10.1093/annonc/mdw004 [doi] PST - ppublish SO - Ann Oncol. 2016 Apr;27(4):680-7. doi: 10.1093/annonc/mdw004. Epub 2016 Jan 22.