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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
European Urology, Volume 70 Issue 3<http://www.europeanurology.com/eu/issue/70/3/volume-70-issue-3-september-2016>, September 2016, Pages 438-444
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.
Design, setting, and participants
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 5 mg of P twice daily, and 1333/2267 received AA (1 g) plus P.
Results and limitations
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.
Keywords: Abiraterone acetate, Adverse events, Corticosteroids, Glucocorticoid, Long term, Metastatic castration-resistant prostate cancer, Tolerability.
a Institut Gustave Roussy, University of Paris Sud, Villejuif, France
b BC Cancer Agency, Vancouver, BC, Canada
c The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK
d Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
e Charité-Universitätsmedizin Berlin, Berlin, Germany
f Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
g Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
h Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA
i Janssen Research & Development, Beerse, Belgium
j Janssen Research & Development, Horsham, PA, USA
k Janssen Scientific Affairs, Horsham, PA, USA
l Janssen Research & Development, Raritan, NJ, USA
m Janssen Research & Development, Los Angeles, CA, USA
n Janssen Global Services, Raritan, NJ, USA
o University of Washington, Seattle, WA, USA
⁎ Corresponding author. Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, 114 Rue Edouard Vaillant, 94800 Villejuif, France. Tel. +33 1 42114317; Fax: +33 1 42115211.
© 2016 European Association of Urology, Published by Elsevier B.V.