title: A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma.
abstract: OBJECTIVE
  Sorafenib, an oral multikinase inhibitor of the VEGFR/PDGFR/Raf/MEK/ERK pathway, has shown potential activity in patients with recurrent ovarian cancer (OC). One strategy to prolong disease control and survival in patients with OC is maintenance therapy after achieving a complete response. A double-blind, randomized, placebo-controlled, phase II study to assess the efficacy and safety of maintenance therapy with sorafenib in the treatment of OC is presented.
  
  
  METHODS
  Patients with epithelial OC or primary peritoneal cancer in complete remission were randomized to sorafenib 400mg BID or matching placebo. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  Of 246 randomized patients, 93% had OC; baseline characteristics were balanced between treatment arms. There was no significant difference between sorafenib and placebo arms for PFS (median 12.7 vs 15.7 months; hazard ratio 1.09; 95% CI 0.72-1.63), although there was a notable imbalance in early censoring. The most common ≥ grade 3 adverse events (AEs) were hand-foot skin reaction (39.0% vs 0.8%) and rash (14.6% vs 0%). More patients receiving sorafenib versus placebo required dose reductions (67.5% vs 30.1%), resulting in a lower than planned median daily dose (median 584.6 vs 800.0mg). Treatment with sorafenib was of shorter duration (median 17.6 vs 51.9 weeks) with more frequent discontinuations due to AEs (37.4% vs 6.5%).
  
  
  CONCLUSIONS
  Sorafenib 400mg BID cannot be recommended as maintenance therapy for patients with OC in complete remission. Assessment of efficacy was limited by the high rate of dose reductions and early discontinuations.
authors.affiliation: Columbia University & NY Presbyterian Hospital, New York, NY 10032, USA. th2135@columbia.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Byoung-Gie
authors.initials: BG
authors.lastname: Kim
authors.forename: Catherine
authors.initials: C
authors.lastname: Lhommé
authors.forename: Janina
authors.initials: J
authors.lastname: Markowska
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.forename: Minghua
authors.initials: M
authors.lastname: Shan
authors.forename: Oana
authors.initials: O
authors.lastname: Petrenciuc
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D010919:Placebos; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib