title: Improvements in Radiographic Progression-Free Survival Stratified by ERG Gene Status in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Abiraterone Acetate.
abstract: OBJECTIVE
  Gene fusions leading to androgen receptor-modulated ERG overexpression occur in up to 70% of metastatic castration-resistant prostate cancers (mCRPC). We assessed the association between ERG rearrangement status and clinical benefit from abiraterone acetate.
  
  
  METHODS
  COU-AA-302 is a phase III trial comparing abiraterone acetate and prednisone versus prednisone in chemotherapy-naïve mCRPC. ERG status was evaluated by FISH on archival tumors. End points included radiographic progression-free survival (rPFS), time to PSA progression (TTPP), rate of ≥50% PSA decline from baseline, and overall survival (OS). Cox regression was used to evaluate association with time-to-event measures and Cochran-Mantel-Haenszel for PSA response.
  
  
  RESULTS
  ERG status was defined for 348 of 1,088 intention-to-treat patients. ERG was rearranged in 121 of 348 patients with confirmed ERG status (35%). Cancers with an ERG fusion secondary to deletion of 21q22 and increased copy number of fusion sequences (class 2+ Edel) had a greater improvement in rPFS after abiraterone acetate and prednisone [22 vs. 5.4 months; HR (95% confidence interval, CI), 0.31 (0.15-0.68); P = 0.0033] than cancers with no ERG fusion [16.7 vs. 8.3 months; 0.53 (0.38-0.74); P = 0.0002] or other classes of ERG rearrangement. There was also greater benefit in this subgroup for TTPP.
  
  
  CONCLUSIONS
  Both ERG-rearranged and wild-type cancers had a significant improvement in rPFS with abiraterone acetate and prednisone in the COU-AA-302 trial. However, our data suggest that 2+ Edel cancers, accounting for 15% of all mCRPC patients and previously associated with a worse outcome, derived the greatest benefit.
authors.affiliation: The Institute of Cancer Research and The Royal Marsden Hospital, London, United Kingdom. gerhardt.attard@icr.ac.uk.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.affiliation: The Institute of Cancer Research and The Royal Marsden Hospital, London, United Kingdom.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Juravinski Cancer Centre and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Som D
authors.initials: SD
authors.lastname: Mukherjee
authors.affiliation: Princess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
authors.affiliation: Ziekenhuisnetwerk Antwerpen-Middelheim Oncology Clinic, Antwerp, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schrijvers
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.affiliation: Janssen Research and Development, Spring House, Pennsylvania.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.affiliation: Janssen Research and Development, Menlo Park, California.
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.affiliation: Janssen Research and Development, Los Angeles, California.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Griffin
authors.affiliation: Janssen Research and Development, San Diego, California.
authors.forename: Thian
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: Janssen Research and Development, Spring House, Pennsylvania.
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Ricci
authors.affiliation: Janssen Research and Development, Spring House, Pennsylvania.
authors.forename: Kathy
authors.initials: K
authors.lastname: Zelinsky
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
mesh_terms: D000069501:Abiraterone Acetate / Q000627:therapeutic use*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: D000970:Antineoplastic Agents; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D000069501:Abiraterone Acetate; D011241:Prednisone