Certainly, men with mCRPC and early progression (≤1 year) or non-response to initial ADT carry a poor prognosis, with no consensus regarding second-line therapy for these patients. Based on the COU-AA-302 trial, we know that abiraterone + prednisone is effective for patients with chemo-naïve mCRPC [1,2], however there is limited data available for ADT poor responders. As such, the objective of this trial was to evaluate the efficacy and safety of abiraterone + prednisolone as secondary treatment (after ADT) for high-risk population.
This trial was a multicenter, open-label, single arm, 2-stage trial [hypothesis: p0=0.150, p1=0.350, α = 0.025, β = 0.100], with 48 patients required to provide an efficacy analysis. Key eligibility criteria include: (i) chemo-naïve mCRPC (testosterone level <50 ng/dL under medical/surgical castration), (ii) age ≥20, and (iii) evidence of PSA progression by PCWG2 criteria ≤1 year or without achieving a normal PSA level (<4 ng/mL) during initial ADT. For eligible patients, 1000 mg abiraterone acetate with 10 mg prednisolone were administered daily until disease progression. The primary endpoint was the proportion of patients achieving a PSA decline of ≥ 50% from baseline after 12 weeks of treatment in accordance with PCWG2 criteria (PSA response rate). There were 50 patients enrolled in this study, and 49 were evaluable for analysis. At baseline, the median age was 73 (range 55–86) years, the median PSA level was 28.34 ng/mL (range 2.28-294.25), and the median duration of initial ADT was 6.4 months (range 1.4 –18.8). 90% of patients had a Gleason sum score ≥8, and all had a treatment history of bicalutamide. PSA response rate was 55% (n = 27/49; 95%CI 41-68), and the PSA decline began after 4 or 8 weeks from baseline. The treatment was well tolerated with <25% of grade ≥3 adverse events.
In conclusion, this study demonstrated initial efficacy among more than half of men using abiraterone + prednisolone for ADT poor responders. The study demonstrated similar efficacy to the Phase III study COU-AA-302 trial (62% of patients with PSA decline ≥ 50% ), which supports the efficacy of abiraterone + prednisolone for ADT poor responders. Abiraterone + prednisolone appears to be a promising treatment for initial ADT poor responders with an acceptable safety profile, however longer follow-up and additional trials may be necessary to assess downstream outcomes including disease progression, prostate-cancer specific mortality and overall survival.
1. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138-148.
2. Rathkopf DE, Smith MR, de Bono JS, et al. Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol. 2014;66(5):815-825.
Speaker: Gaku Arai, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, Japan
Co-Authors: M. Ogi (Tokyo, Japan) K. Kobayashi (Kanagawa, Japan) N. Okuno (Kanagawa, Japan) T. Takahara (Tokyo, Japan) K. Fukushima (Tokyo, Japan) K. Yoshizawa (Tokyo, Japan)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain