Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.
In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302. Prostate-specific antigen (PSA) response was assessed. Median time to PSA progression was estimated using the Kaplan-Meier method. The PSA response rate (≥50% PSA decline, unconfirmed) was 44% and 67%, respectively. The median time to PSA progression was 3.9 mo (range 2.6-not estimable) for subsequent abiraterone acetate plus prednisone and 2.8 mo (range 1.8-not estimable) for subsequent enzalutamide. The majority of patients (68%) received intervening chemotherapy before subsequent abiraterone acetate plus prednisone or enzalutamide. While acknowledging the limitations of post hoc analyses and high censoring (>75%) in both treatment groups, these results suggest that subsequent therapy with abiraterone acetate plus prednisone or enzalutamide for patients who progressed on abiraterone acetate is associated with limited clinical benefit.



This analysis showed limited clinical benefit for subsequent abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castration-resistant prostate cancer following initial treatment with abiraterone acetate plus prednisone. This analysis does not support prioritization of subsequent abiraterone acetate plus prednisone or enzalutamide following initial therapy with abiraterone acetate plus prednisone.
Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA. Electronic address: smith.matthew@mgh.harvard.edu.
Matthew R
MR
Smith
University of Montréal, Montréal, Québec, Canada.
Fred
F
Saad
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College New York, NY, USA.
Dana E
DE
Rathkopf
Radboud University Medical Centre, Nijmegen, The Netherlands.
Peter F A
PFA
Mulders
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.
Eric J
EJ
Small
Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA.
Neal D
ND
Shore
Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
Karim
K
Fizazi
Janssen Research & Development, San Diego, CA, USA.
Thian
T
Kheoh
Johnson & Johnson Medical China, Shanghai, China.
Jinhui
J
Li
Janssen Research & Development, Beerse, Belgium.
Peter
P
De Porre
Janssen Global Services, Raritan, NJ, USA.
Mary B
MB
Todd
Janssen Research & Development, Los Angeles, CA, USA.
Margaret K
MK
Yu
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Charles J
CJ
Ryan
D000069501:Abiraterone Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects*; D065088:Steroid Synthesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D065088:Steroid Synthesis Inhibitors; D010669:Phenylthiohydantoin; C540278:enzalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; D011241:Prednisone
Abiraterone acetate; Androgen signaling–directed therapy; Chemotherapy-naïve; Metastatic castration-resistant prostate cancer; Sequencing