title: Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC).
abstract: This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone.
  
  
  
  Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile.
  
  
  
  A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm.
  
  
  
  AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.
authors: *Department of Clinical Oncology, Tuen Mun Hospital †Division of Biostatistics and Centre for Clinical Research and Biostatistics, Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong ‡Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital §Department of Clinical Oncology, Queen Mary Hospital ∥Department of Clinical Oncology, Princess Margaret Hospital, Hong Kong ¶Aegera Therapeutics (Pharmascience Inc.), Montreal, QC, Canada.
authors: Francis A S
authors: FA
authors: Lee
authors: Benny Chung-Ying
authors: BC
authors: Zee
authors: Foon Yiu
authors: FY
authors: Cheung
authors: Philip
authors: P
authors: Kwong
authors: Chi Leung
authors: CL
authors: Chiang
authors: Kwong Chuen
authors: KC
authors: Leung
authors: Steven W K
authors: SW
authors: Siu
authors: Conrad
authors: C
authors: Lee
authors: Maria
authors: M
authors: Lai
authors: Chloe
authors: C
authors: Kwok
authors: Marc
authors: M
authors: Chong
authors: Jacques
authors: J
authors: Jolivet
authors: Steward
authors: S
authors: Tung
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009841:Oligonucleotides / Q000627:therapeutic use*; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D000077157:Sorafenib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C498209:AEG 35156; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib