Background 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. Objective 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. Intervention 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. Conclusions 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. Patient summary 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.
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Taken together, the results reported here support those of previous studies demonstrating that long-term treatment with AA plus low-dose P is well tolerated. Our results also show that the incidence of CA-AEs in patients with mCRPC after long-term administration of low-dose P is low and manageable. Author contributions: Karim Fizazi had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Fizazi, de Bono, Scher, De Porre, Londhe, McGowan, Pelhivanov, Charnas, Todd. Acquisition of data: Fizazi, Chi, de Bono, Gomella, Miller, Rathkopf, Ryan, Scher, Shore, Montgomery. Analysis and interpretation of data: Fizazi, De Porre, Londhe, McGowan, Pelhivanov, Charnas, Todd. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Londhe. Obtaining funding: De Porre, Todd. Administrative, technical, or material support: De Porre, Todd. Supervision: De Porre. Other: None. Financial disclosures: Karim Fizazi certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Karim Fizazi has participated in advisory boards and served as a speaker for Janssen. Kim N. Chi has served as a consultant/advisor to Amgen, Astellas Pharma, Bayer, ESSA, Janssen Pharmaceuticals, Lilly/ImClone, Sanofi, and Takeda; has received honoraria from Astellas Pharma, Janssen Pharmaceuticals, and Sanofi; and has received research funding from Amgen, Astellas Pharma, Bayer, Exelixis, Janssen Pharmaceuticals, Novartis, Oncogenex, Sanofi, Teva, and Tokai Pharmaceuticals. Johann S. de Bono is a paid employee of The Institute of Cancer Research, which has a commercial interest in abiraterone acetate, and has served as a paid consultant for Johnson & Johnson. Leonard G. Gomella has served as a consultant/advisor to Astellas Pharma, Bayer, Dendreon, and Janssen Pharmaceuticals; and has received research funding from Astellas Pharma and Janssen Pharmaceuticals. Kurt Miller has served as a consultant/advisor to and received research funding from Amgen, Bayer, BMS, Ferring, Dendreon, GSK, Astellas Pharma, Janssen Pharmaceuticals, Merck, Novartis, Pfizer, and Roche. Dana E. Rathkopf has served as a consultant/advisor to and received research funding from Janssen Research & Development, AstraZeneca, Celgene, Ferring, Medication, Millenium/Takeda, and Novartis. Charles J. Ryan has received honoraria from Janssen Research & Development. Howard I. Scher has served as a paid consultant/advisor to Amgen, BIND Pharmaceuticals, Blue Earth Diagnostics, Chugai Academy for Advanced Oncology, Dendreon, Elsevier's PracticeUpdate Website, Endo/Orion Pharmaceuticals, Enzon, Ferring Pharmaceuticals, Genentech, ImClone, Johnson & Johnson, Light Oncology Sciences, MED IQ, Medivation, Millennium, Novartis, OncologySTAT, Ortho Biotech Oncology Research and Development, Roche, Roche (Genentech), Sanofi-Aventis, and WCG Oncology; has served as an unpaid consultant/advisor to Aragon, Astellas, AstraZeneca, Bristol-Myers Squibb, Celgene, Endocyte, Exelixis, Foundation Medicine, Genentech, Janssen Pharmaceuticals, Janssen Research (Veridex), Novartis, Pfizer (Biologic), Takeda Millennium, and Ventana (Member of the Roche Group); has received honoraria from Chugai Academy for Advanced Oncology; and has received research funding to the Memorial Sloan Kettering Cancer Center from Agensys, Aragon, BIND Therapeutics, Bristol-Myers Squibb, Exelixis, Guardant Health, Genentech, Innocrin Pharma, Janssen Diagnostics, Janssen Pharmaceuticals, and Medivation. Neal D. Shore is a consultant/advisor to Algeta, Amgen, Bayer, BNI, Dendreon, Ferring, Janssen, Millennium, and Sanofi. Peter De Porre, Anil Londhe, Nonko Pehlivanov, Robert Charnas, and Mary B. Todd are employees of Janssen Research & Development and hold stock options in Johnson & Johnson. Tracy McGowan is an employee of Janssen Scientific Affairs and holds stock options in Johnson & Johnson. Bruce Montgomery has received research funding from Janssen Research & Development. Funding/Support and role of the sponsor: This study was funded by Janssen Research & Development (formerly Ortho Biotech Oncology Research & Development, unit of Cougar Biotechnology). The sponsor played a role in the design and conduct of the study; in the collection, management, analysis, and interpretation of data; and in the preparation, review, and approval of the manuscript. Acknowledgments: Writing assistance was provided by Lashon Pringle of PAREXEL and was funded by Janssen Global Services LLC.
© 2016 European Association of Urology
- Abiraterone acetate
- Adverse events
- Long term
- Metastatic castration-resistant prostate cancer