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

Matthew R Smith; Fred Saad; Dana E Rathkopf; Peter F A Mulders; Johann S de Bono; Eric J Small; Neal D Shore; Karim Fizazi; Thian Kheoh; Jinhui Li; Peter De Porre; Mary B Todd; Margaret K Yu; Charles J Ryan

doi:10.1016/j.eururo.2017.03.007

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

Eur Urol. 2017 Jul;72(1):10-13. doi: 10.1016/j.eururo.2017.03.007. Epub 2017 Mar 15.

Authors

Matthew R Smith¹, Fred Saad², Dana E Rathkopf³, Peter F A Mulders⁴, Johann S de Bono⁵, Eric J Small⁶, Neal D Shore⁷, Karim Fizazi⁸, Thian Kheoh⁹, Jinhui Li¹⁰, Peter De Porre¹¹, Mary B Todd¹², Margaret K Yu¹³, Charles J Ryan⁶

Affiliations

¹ Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA. Electronic address: smith.matthew@mgh.harvard.edu.
² University of Montréal, Montréal, Québec, Canada.
³ Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College New York, NY, USA.
⁴ Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵ The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK.
⁶ Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
⁷ Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA.
⁸ Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
⁹ Janssen Research & Development, San Diego, CA, USA.
¹⁰ Johnson & Johnson Medical China, Shanghai, China.
¹¹ Janssen Research & Development, Beerse, Belgium.
¹² Janssen Global Services, Raritan, NJ, USA.
¹³ Janssen Research & Development, Los Angeles, CA, USA.

PMID: 28314611
DOI: 10.1016/j.eururo.2017.03.007

Abstract

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.

Patient summary: 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.

Keywords: Abiraterone acetate; Androgen signaling–directed therapy; Chemotherapy-naïve; Metastatic castration-resistant prostate cancer; Sequencing.

MeSH terms

Abiraterone Acetate / adverse effects
Abiraterone Acetate / therapeutic use*
Antineoplastic Agents, Hormonal / adverse effects
Antineoplastic Agents, Hormonal / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Benzamides
Clinical Trials, Phase III as Topic
Disease Progression
Disease-Free Survival
Drug Resistance, Neoplasm
Humans
Kallikreins / blood
Kaplan-Meier Estimate
Male
Multicenter Studies as Topic
Neoplasm Metastasis
Nitriles
Phenylthiohydantoin / adverse effects
Phenylthiohydantoin / analogs & derivatives*
Phenylthiohydantoin / therapeutic use
Prednisone / adverse effects
Prednisone / therapeutic use*
Prostate-Specific Antigen / blood
Prostatic Neoplasms, Castration-Resistant / blood
Prostatic Neoplasms, Castration-Resistant / drug therapy*
Prostatic Neoplasms, Castration-Resistant / mortality
Prostatic Neoplasms, Castration-Resistant / pathology
Randomized Controlled Trials as Topic
Retrospective Studies
Risk Factors
Signal Transduction / drug effects*
Steroid Synthesis Inhibitors / adverse effects
Steroid Synthesis Inhibitors / therapeutic use*
Time Factors
Treatment Outcome

Substances

Antineoplastic Agents, Hormonal
Benzamides
Nitriles
Steroid Synthesis Inhibitors
Phenylthiohydantoin
enzalutamide
KLK3 protein, human
Kallikreins
Prostate-Specific Antigen
Abiraterone Acetate
Prednisone