Karim Fizazi1, Kim N Chi2, Johann S de Bono3, Leonard G Gomella4, Kurt Miller5, Dana E Rathkopf6, Charles J Ryan7, Howard I Scher6, Neal D Shore8, Peter De Porre9, Anil Londhe10, Tracy McGowan11, Nonko Pelhivanov12, Robert Charnas13, Mary B Todd14, Bruce Montgomery15. 1. Institut Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: karim.fizazi@igr.fr. 2. BC Cancer Agency, Vancouver, BC, Canada. 3. The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK. 4. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. 5. Charité-Universitätsmedizin Berlin, Berlin, Germany. 6. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. 7. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. 8. Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA. 9. Janssen Research & Development, Beerse, Belgium. 10. Janssen Research & Development, Horsham, PA, USA. 11. Janssen Scientific Affairs, Horsham, PA, USA. 12. Janssen Research & Development, Raritan, NJ, USA. 13. Janssen Research & Development, Los Angeles, CA, USA. 14. Janssen Global Services, Raritan, NJ, USA. 15. University of Washington, Seattle, WA, USA.
Abstract
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 5mg of P twice daily, and 1333/2267 received AA (1g) 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.
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 5mg of P twice daily, and 1333/2267 received AA (1g) 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.
Authors: Johann S de Bono; Christopher J Logothetis; Arturo Molina; Karim Fizazi; Scott North; Luis Chu; Kim N Chi; Robert J Jones; Oscar B Goodman; Fred Saad; John N Staffurth; Paul Mainwaring; Stephen Harland; Thomas W Flaig; Thomas E Hutson; Tina Cheng; Helen Patterson; John D Hainsworth; Charles J Ryan; Cora N Sternberg; Susan L Ellard; Aude Fléchon; Mansoor Saleh; Mark Scholz; Eleni Efstathiou; Andrea Zivi; Diletta Bianchini; Yohann Loriot; Nicole Chieffo; Thian Kheoh; Christopher M Haqq; Howard I Scher Journal: N Engl J Med Date: 2011-05-26 Impact factor: 91.245
Authors: Karim Fizazi; Howard I Scher; Arturo Molina; Christopher J Logothetis; Kim N Chi; Robert J Jones; John N Staffurth; Scott North; Nicholas J Vogelzang; Fred Saad; Paul Mainwaring; Stephen Harland; Oscar B Goodman; Cora N Sternberg; Jin Hui Li; Thian Kheoh; Christopher M Haqq; Johann S de Bono Journal: Lancet Oncol Date: 2012-09-18 Impact factor: 41.316
Authors: Marie-Hélène Lafeuille; Jonathan Gravel; Amanda Grittner; Patrick Lefebvre; Lorie Ellis; R Scott McKenzie Journal: Am Health Drug Benefits Date: 2013-07
Authors: Dana E Rathkopf; Matthew R Smith; Johann S de Bono; Christopher J Logothetis; Neal D Shore; Paul de Souza; Karim Fizazi; Peter F A Mulders; Paul Mainwaring; John D Hainsworth; Tomasz M Beer; Scott North; Yves Fradet; Hendrik Van Poppel; Joan Carles; Thomas W Flaig; Eleni Efstathiou; Evan Y Yu; Celestia S Higano; Mary-Ellen Taplin; Thomas W Griffin; Mary B Todd; Margaret K Yu; Youn C Park; Thian Kheoh; Eric J Small; Howard I Scher; Arturo Molina; Charles J Ryan; Fred Saad Journal: Eur Urol Date: 2014-03-06 Impact factor: 20.096
Authors: Jimmy L Zhao; Karim Fizazi; Fred Saad; Kim N Chi; Mary-Ellen Taplin; Cora N Sternberg; Andrew J Armstrong; Johann S de Bono; William T Duggan; Howard I Scher Journal: Clin Cancer Res Date: 2022-03-01 Impact factor: 13.801
Authors: Lillian Y Lai; Mary K Oerline; Megan E V Caram; Phoebe A Tsao; Samuel R Kaufman; Brent K Hollenbeck; Vahakn B Shahinian Journal: J Natl Cancer Inst Date: 2022-08-08 Impact factor: 11.816
Authors: Giandomenico Roviello; Maria Rosa Cappelletti; Laura Zanotti; Angela Gobbi; Chiara Senti; Alberto Bottini; Andrea Ravelli; Alberto Bonetta; Giovanni Paganini; Daniele Generali Journal: Medicine (Baltimore) Date: 2016-10 Impact factor: 1.889
Authors: E David Crawford; Neal D Shore; Daniel P Petrylak; Celestia S Higano; Charles J Ryan Journal: Ther Adv Med Oncol Date: 2017-03-22 Impact factor: 8.168