WASHINGTON, DC USA (UroToday.com) - This presentation provides long-term efficacy results from the initial MDV3100 phase I-II trial. It suggests that the antitumor activity of MDV3100 is of long duration.
MDV3100 is a novel androgen receptor (AR) antagonist. It is previously reported that MDV3100 slows growth and induces cell death in bicalutamide-resistant tumors via 3 complementary actions: AR direct antagonism, inhibition of nuclear translocation of the AR complex, and inhibition of DNA binding by the AR. In vitro, AR partial agonism has not been seen with MDV3100 unlike first generation anti-androgens. Reported in this presentation is the long-term follow-up for time to prostate-specific antigen (PSA) and radiographic progression from the initial study.
In the Phase I-II trial, patients with progressive CRPC were enrolled in sequential cohorts of 3-6 patients ; MDV3100 doses were 30, 60, 150, 240, 360, 480, and 600 mg/day. After confirming dose tolerability, enrollment was expanded to include approximately 24 pts per dose cohort who were chemotherapy-naive (chemo-naive; n=12) or previously treated with docetaxel (post-chemo; n=12).
A total of 140 patients were enrolled, 18 (13%) who continue on active treatment (chemo-naive, n=16; post-chemo, n=2) with a median of 131 weeks of therapy. The median time on treatment is 51 weeks for chemo-naive and 17 weeks for post-chemo patients. The median time to PSA progression, defined as a >25% increase in PSA from baseline, was not met for chemo-naive pts and was 33 weeks for post-chemo pts. Median time to PSA progression by Prostate Cancer Clinical Trials Working Group 2 criteria was 41 and 20 weeks for chemo-naive and post-chemo pts, respectively. Phase III trials with MDV3100 are presently underway in chemo-naive and post-chemo patients.
Presented by Howard Scher, et al. at the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.