title: Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer.
abstract: BACKGROUND
  There is an urgent need for qualified predictive biomarkers of sensitivity for the treatments used in patients with castration-resistant prostate cancer (CRPC). We attempted to identify ready-to-use clinical predictors of improved outcome in metastatic CRPC (mCRPC) patients treated with next generation androgen receptor (AR) axis targeted drugs.
  
  
  METHODS
  We reviewed a cohort of patients who received AR axis targeted drugs for CRPC at two major French cancer centres. The predictive role of several clinical, biological and radiological parameters on progression-free survival (PFS) was studied.
  
  
  RESULTS
  The study cohort consisted of 173 patients. Median duration of response to initial androgen deprivation therapy (ADT) (time to castration resistance, TTCRPC) was 17.8 months. The 50% prostate-specific antigen (PSA) response rate to AR axis targeted drugs was 16% (95% confidence interval (CI): 6-27) and 41% (95% CI: 30-47) in patients with TTCRPC of under and over 12 months respectively (p=0.005). Median PFS was 2.8 months (95% CI: 2.1-3.9) and 5.8 (95% CI: 4.6-7.8; HR: 0.58, p=0.002). In patients treated with post-docetaxel enzalutamide (n=57), median PFS was 2.8 months and 8.6 months, (Hazard ratio (HR)=3.1; 95% CI: 1.6-5.8, p=0.0016) according to TTCRPC, whereas no difference was observed in placebo-treated patients (n=27). The 50% PSA response rate to enzalutamide was 8% (95% CI: 0-38) and 58% (95% CI: 42-73) in patients with a TTCRPC of under and over 12 months respectively (p<0.001).
  
  
  CONCLUSIONS
  The previous duration of response to ADT is a predictor of sensitivity to next generation AR axis targeted drugs in patients with mCRPC.
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France. Electronic address: yohann.loriot@gustaveroussy.fr.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Institut Jean Godinot, Reims, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Eymard
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Patrikidou
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France.
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Ileana
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Di Palma
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: Androgen receptor; Endocrine therapy; Predictive factors; Prostate cancer; Time to castration resistance