Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies.
The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).



To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity.



Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-naïve mCRPC (COU-AA-302) patients receiving AA. The treatment effect on overall survival (OS), radiographic progression-free survival (rPFS), and prostate-specific antigen (PSA) response analysed by quartile duration of prior gonadotropin-releasing hormone agonists (GnRHa) or androgen receptor (AR) antagonist.



Patients were randomised to AA (1000mg, orally once daily) plus prednisone (5mg, orally twice daily) or placebo plus prednisone. Prior endocrine therapy was GnRHa (COU-AA-301, n=1127 [94%]; COU-AA-302, n=1057 [97%], 45.1 mo or 36.7 mo median duration, respectively) and/or orchiectomy (COU-AA-301, n=78 [7%] COU-AA-302, n=44 [4%]); castrated patients received prior AR antagonists (COU-AA-301, n=1015 [85%]; COU-AA-302, n=1078 [99%], 15.7 mo or 16.1 mo median duration, respectively).



Cox model was used to obtain hazard ratio and associated 95% confidence interval with statistical inference by log rank statistic.



Clinical benefit with AA was observed for OS, rPFS, and PSA response for nearly all quartiles with GnRHa or AR antagonists in both COU-AA-301 and COU-AA-302. In COU-AA-301, patients with a longer duration of prior endocrine therapy tended to have greater AA OS, rPFS, and PSA response benefit, with lead-time chemotherapy bias potentially impacting COU-AA-301 results. Time to castration resistance was not captured. This analysis is limited as a post-hoc exploratory analysis.



In the COU-AA-301 and COU-AA-302 studies, AA produced clinical benefits regardless of prior endocrine therapy duration in patients with mCRPC.



Metastatic castration-resistant prostate cancer patients derived clinical benefits with abiraterone acetate regardless of prior endocrine therapy duration.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: Joaquim_Bellmunt@dfci.harvard.edu.
Joaquim
J
Bellmunt
Janssen Research & Development, San Diego, CA, USA.
Thian
T
Kheoh
Janssen Research & Development, Los Angeles, CA, USA.
Margaret K
MK
Yu
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Matthew R
MR
Smith
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Eric J
EJ
Small
Radboud University Medical Centre, Nijmegen, The Netherlands.
Peter F A
PF
Mulders
Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
Karim
K
Fizazi
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Dana E
DE
Rathkopf
University of Montréal, Montréal, Québec, Canada.
Fred
F
Saad
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Howard I
HI
Scher
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Mary-Ellen
ME
Taplin
Monash University and Eastern Health, Victoria, Australia.
Ian D
ID
Davis
ZNA Middelheim Oncology Clinic, Medical Oncology, Antwerp, Belgium.
Dirk
D
Schrijvers
Churchill Hospital, Oxford, UK.
Andrew
A
Protheroe
Janssen Research & Development, Menlo Park, CA, USA.
Arturo
A
Molina
Janssen Research & Development, Beerse, Belgium.
Peter
P
De Porre
Janssen Research & Development, Los Angeles, CA, USA.
Thomas W
TW
Griffin
The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK.
Johann S
JS
de Bono
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Charles J
CJ
Ryan
Georges Pompidou Hospital, University René Descartes, Paris, France.
Stéphane
S
Oudard
D000069501:Abiraterone Acetate / Q000008:administration & dosage; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D019233:Retreatment; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use
D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D043823:Taxoids; D000077143:Docetaxel; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; D011241:Prednisone
Abiraterone acetate; Androgen receptor antagonists; Gonadotropin-releasing hormone; Prednisone; Prostate cancer