STOCKHOLM, SWEDEN (UroToday.com) - Abiraterone acetate (AA) is a potent CYP17 inhibitor that inhibits persistent andrenal and intratumoral androgen synthesis. In the phase 3 COU-AA-302 trial, AA + prednisone (P) significantly improved radiographic progression-free survival (rPFS), improved overall survival (OS), and significantly delayed clinical decline and time to opiate use and chemotherapy in patients with asymptomatic or mildly symptomatic metastatic CRPC (mCRPC). The authors performed an exploratory analysis to determine the impact of duration of prior endocrine therapy with either gonadotropin-releasing hormone (GnRH) agonists or androgen receptor (AR) inhibitors on clinical benefit of AA in 3 COU-AA-302.
Of 1 088 total patients, nearly all received prior endocrine therapy with either GnRH agonists (97%) or AR inhibitors (99%). The median duration of prior GnRH agonists and AR inhibitors was 36.7 months and 16.1 months, respectively. Time to rPFS was significantly longer in the AA + P arm versus the P alone arm in patients for the subgroups above or below median duration of prior endocrine therapy with GnRH agonists or AR inhibitors. rPFS benefit with AA + P versus P alone was observed regardless of duration of prior endocrine therapy with either prior GnRH agonists or AR. Clinical benefit with AA + P versus P alone was demonstrated by significantly improved rPFS regardless of whether patients had exposure to prior endocrine therapy above or below the median duration for GnRH agonists or AR inhibitors, respectively.
Clinical benefit was also observed when patients were divided into quartiles by duration of prior endocrine therapy. Clinical benefit was observed in patients in the lowest quartile with the shortest duration of prior endocrine therapy, which may indicate benefit in patients least sensitive to prior endocrine therapy—however, there were too few patients to specifically examine the patient subpopulation within the lowest quartile with 6 to 12 months of prior endocrine therapy. Longer exposure of prior endocrine therapy was associated with longer time to rPFS, regardless of treatment assignment.
Presented by D. Schrijvers at the 29th Annual European Association of Urology (EAU) Congress - April 11 - 15, 2014 - Stockholmsmässan - Stockholm, Sweden.
ZNA Middelheim Oncology Clinic, Dept. of Medical Oncology, Antwerp, Belgiumn
Written by Jeffrey J.Tomaszewski, MD, medical writer for UroToday.com
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