title: Orteronel Switch Maintenance Therapy in Metastatic Castration Resistant Prostate Cancer After First-Line Docetaxel: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial (SAKK 08/11).
abstract: We tested whether a switch maintenance treatment with orteronel, an oral inhibitor of androgen biosynthesis, prolongs disease control in men with metastatic castration-resistant prostate cancer (mCRPC) after documented disease stabilization with docetaxel.
  
  
  
  Men with mCRPC and non-progressive disease after a cumulative dose of ≥300 mg/m2docetaxel for first line treatment were randomized 1:1 to receive orteronel 300 mg twice daily or placebo. The primary endpoint was event-free survival (EFS) defined as the time from randomization to death or the combination of at least two of radiographic, clinical, or PSA progression. Ninety-six patients per arm were planned to demonstrate an improvement of median EFS from 4 months on placebo to 6.7 months on orteronel (hazard ratio (HR) 0.6; type I error 5% and power 90%).
  
  
  
  Forty-seven patients (23 orteronel, 24 placebo) were randomized before premature closure of the trial because of discontinuation of clinical development of orteronel. Median EFS was 8.5 months with orteronel and 2.9 months with placebo (P = 0.001; HR 0.32; 95%CI 0.15-0.65). Median radiographic progression-free survival (rPFS) was 8.5 and 2.8 months (P = 0.02; HR 0.42; 95%CI 0.20-0.91) in the orteronel and placebo arm, respectively. PSA decline ≥50% was seen in 57% on orteronel and 4% on placebo. Toxicity was mainly mild, one patient on orteronel developed transient grade 3 adrenal insufficiency and one grade 4 pneumonitis.
  
  
  
  Orteronel significantly prolongs EFS in men with mCRPC who achieve disease stabilization with docetaxel. The concept of switch maintenance therapy in mCRPC warrants further research. Prostate 76:1519-1527, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland. richard.cathomas@ksgr.ch.
authors.forename: Richard
authors.initials: R
authors.lastname: Cathomas
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Crabb
authors.affiliation: Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Mark
authors.affiliation: Department of Oncology Kantonsspital Luzern, Luzern, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Winterhalder
authors.affiliation: Department of Oncology/Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Rothermundt
authors.affiliation: Department of Oncology, The Christie Clinic, Manchester, United Kingdom.
authors.forename: Tony
authors.initials: T
authors.lastname: Elliott
authors.affiliation: Department of Oncology, Kantonsspital Aargau, Aarau, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: von Burg
authors.affiliation: SAKK Coordinating Center, Bern, Switzerland.
authors.forename: Heike
authors.initials: H
authors.lastname: Kenner
authors.affiliation: SAKK Coordinating Center, Bern, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hayoz
authors.affiliation: SAKK Coordinating Center, Bern, Switzerland.
authors.forename: Simona Berardi
authors.initials: SB
authors.lastname: Vilei
authors.affiliation: Oncology, Hospital Simmental, Thun, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauch
authors.affiliation: Department of Oncology, Bellinzona IOSI, Bellinzona, Switzerland.
authors.forename: Enrico
authors.initials: E
authors.lastname: Roggero
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Mohaupt
authors.affiliation: International Breast Cancer Study Group Coordinating Center Bern and University Hospital, Inselspital Bern, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bernhard
authors.affiliation: Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Manetsch
authors.affiliation: Department of Oncology/Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Silke
authors.initials: S
authors.lastname: Gillessen
mesh_terms: D000368:Aged; D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D010147:Pain Measurement; D010919:Placebos; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011788:Quality of Life; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D007093:Imidazoles; D009281:Naphthalenes; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; C571806:orteronel
keywords: castration-resistant prostate cancer; docetaxel; maintenance; orteronel