ORLANDO, FL, USA (UroToday.com) - Visceral disease (VD) associated with liver metastases is a negative prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) and may be less responsive to hormonal therapy.
Abiraterone acetate (AA) is a selective androgen biosynthesis inhibitor that inhibits androgen synthesis from adrenal and intratumoral sources by blocking the action of CYP17. AA was approved by the FDA based on study COU-AA-301 for men with mCRPC after docetaxel (D) where AA plus prednisone (P) showed a significant improvement in overall survival (OS) compared to placebo. The indication was recently expanded to include chemo-naïve mCRPC patients after study COU-AA-302 demonstrated favorable results for AA plus P compared to placebo.
This post-hoc exploratory analysis is trying to determine if the clinical benefits seen in COU-AA-301 on OS and other clinical outcomes are maintained in post-chemo mCRPC patients with VD (liver or lung, but not nodal only metastases).
In COU-AA-301, patients with mCRPC previously treated with D were randomized 2:1 to AA (1000 mg) plus P (5mg bid) (n=797) or placebo plus P (5 mg bid) (n=398). Outcomes in this post-hoc exploratory study of the VD subset included OS, radiographic progression-free survival (rPFS), PSA response rate, and objective response rate. Results shown here represent an updated analysis (775 events) of patients with (n=352) or without (n=843) VD. The treatment groups were well balanced for patients with and without VD. Patients with VD showed more advanced disease, especially those with liver metastases as shown by baseline PSA and circulating tumor cell (CTC) levels. The median duration of treatment was 5.5 months for the AA plus P group and 3.1 months for the placebo group in patients with VD; the values were 8.2 and 3.7 months respectively in patients without VD. The OS benefit of AA plus P was similarly improved compared with placebo in patients with VD (4.6 months) and without VD (4.8 months). Treatment with AA plus P showed significant reductions in the risk of radiographic progression or death in patients with VD (40%) or without VD (32%). PSA response rates (50% reduction) were significantly improved by AA plus P in both groups. Objective response rates were superior with AA plus P in both groups. In patients with liver metastases only, median OS was much shorter compared with lung metastases only; however, OS was longer in both groups treated with AA plus P. The objective response rate was worse in patients with liver metastases compared with lung metastases, but improved with AA plus P in both groups. Grade 3/4 adverse events (AEs) were similar in both groups.
To conclude, VD is associated with a worse prognosis but the absolute OS benefit favoring AA plus P was similar in patients with VD and without VD. The anti-tumor activity with AA is significant, and AA provides clinical benefit including improvements in OS and rPFS in post-D mCRPC patients with VD. This data indicates that AA plus P is a therapeutically active treatment option for mCRPC patients, even for those patients with more severe disease associated with liver metastases. Safety and tolerability of AA plus P in patients with VD was similar to what has been reported previously in mCRPC.
Presented by Oscar B. Goodman Jr.,1 Thomas W. Flaig,2 Arturo Molina,3 Peter F.A. Mulders,4 Henrik Suttmann,5 Jinhui Li,6 Thian Kheoh,3 Johann S. de Bono,7 and Howard I. Scher8 at the 2013 Genitourinary Cancers Symposium - February 14 - 16, 2013 - Rosen Shingle Creek - Orlando, Florida USA
1Comprehensive Cancer Centers of Nevada, Las Vegas, NV; 2University of Colorado Cancer Center, Aurora, CO; 3Janssen Research & Development, Los Angeles, CA; 4Radboud University Medical Centre, Nijmegen, The Netherlands; 5Urologikum Hamburg, Hamburg, Germany; 6Janssen Research & Development, Raritan, NJ; 7Institute of Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom; 8Memorial Sloan-Kettering Cancer Center and Weill-Cornell Medical College, New York, NY
Written by Anna Forsberg, medical reporter for UroToday.com
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