Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer

Abiraterone acetate (AA) is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis and prolongs the survival of patients with metastatic castration-resistant prostate cancer (mCRPC).

AA plus prednisone (P) (AA+P) is approved for the treatment of patients with mCRPC.

To investigate whether long-term use of low-dose P with or without AA leads to corticosteroid-associated adverse events (CA-AEs) in mCRPC patients.

The study included 2267 patients in COU-AA-301 and COU-AA-302. We used an inclusive Standardized MedDRA Queries-oriented approach to identify 112 preferred terms for known CA-AEs, and assessed the incidence of CA-AEs during 3-mo exposure intervals and across all P exposure levels.

All 2267 patients received 5mg of P twice daily, and 1333/2267 received AA (1g) plus P.

The CA-AE incidence after any P exposure was 25%, 26%, and 23% for any grade, and 5%, 5%, and 4% for grade ≥3 CA-AEs for all patients and the AA+P and P alone groups, respectively. The most common any-grade CA-AEs were hyperglycemia (7.4%, 7.8%, and 6.9% for all patients, AA+P, and P alone, respectively) and weight increase (4.3%, 3.9%, and 4.8%, respectively). When assessed by duration of exposure (3-mo intervals up to ≥30 mo), no discernable trend was observed for CA-AEs, including hyperglycemia and weight increase. The investigator-reported study discontinuation rate due to CA-AEs was 11/2267 (0.5%), and one patient had a CA-AE resulting in death.

Low-dose P given with or without AA is associated with low overall incidence of CA-AEs. The frequency of CA-AEs remained low with increased duration of exposure to P.

We assessed adverse events in patients with metastatic castration-resistant prostate cancer during long-term treatment with a low dose of a corticosteroid. We found that long-term treatment with this low-dose corticosteroid is safe and tolerable.

European urology. 2016 Mar 07 [Epub ahead of print]

Karim Fizazi, Kim N Chi, Johann S de Bono, Leonard G Gomella, Kurt Miller, Dana E Rathkopf, Charles J Ryan, Howard I Scher, Neal D Shore, Peter De Porre, Anil Londhe, Tracy McGowan, Nonko Pelhivanov, Robert Charnas, Mary B Todd, Bruce Montgomery

Institut Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: ., BC Cancer Agency, Vancouver, BC, Canada., The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK., Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA., Charité-Universitätsmedizin Berlin, Berlin, Germany., Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA., Janssen Research & Development, Beerse, Belgium., Janssen Research & Development, Horsham, PA, USA., Janssen Scientific Affairs, Horsham, PA, USA., Janssen Research & Development, Raritan, NJ, USA., Janssen Research & Development, Los Angeles, CA, USA., Janssen Global Services, Raritan, NJ, USA., University of Washington, Seattle, WA, USA.