MDV3100 induces cell death in bicalutamide-resistant tumors via three actions on AR: direct antagonism, inhibition of nuclear translocation of the AR complex, and inhibition of the AR from binding to DNA. MDV3100 has no AR agonist activity in laboratory studies. In patients, preliminary antitumor activity and adverse events have been reported in advanced CaP from a phase 1-2 study of MDV3100. Dr. Mohammad Hirmand presented the long-term follow-up for time to PSA and radiographic progression.
Patients with progressive castration-resistant prostate cancer (CRPC) were enrolled in sequential cohorts of 3 to 6 patients of MDV3100 doses of 30, 60, 150, 240, 360, 480, and 600 mg/day. After confirming dose tolerability, enrollment was expanded for doses ≥60 mg/day to include approximately 24 patients (n=12/group) per cohort who were either chemotherapy-naïve (naïve) or previously treated with docetaxel (post-chemotherapy). One hundred forty patients were enrolled and 18 (13%) continued on active treatment (naïve, n = 16; post-chemotherapy, n = 2) at a median of 131 weeks after starting therapy. Long-term follow-up results demonstrate that median time to PSA progression (when defined as a 25% increase in PSA from baseline) was not reached in naïve patients and was 33 weeks in post-chemo men. PSA progression (when defined as Prostate Cancer Working Group 2 definition) was 41 weeks in naïve patients and was 20 weeks in post-chemo men. Median time to radiographic progression was 56 and 24 weeks in naïve patients and post-chemo men, respectively. CTC counts were available in 128 of 140 patients of whom 91% (70/77) of patients with favorable pre-treatment CTC counts remained favorable post-treatment, whereas 49% (25/51) converted from unfavorable pre-treatment status to favorable post-treatment status. MDV3100 is presently under evaluation in 2 ongoing global phase 3 studies in patients with advanced progressive CaP: the AFFIRM study in patients previously treated with docetaxel, and the PREVAIL study in asymptomatic or mildly symptomatic chemotherapy-naïve patients who have progressed following androgen deprivation therapy.
Presented by Mohammad Hirmand, MD, et al. at the 26th Annual European Association of Urology (EAU) Congress - March 18 - 21, 2011 - Austria Centre Vienna, Vienna, Austria