Antitumor activity of MDV3100 in pre- and post-docetaxel advanced prostate cancer: Long-term follow-up of a phase I/II study.

Abstract

134 Background: MDV3100 is a novel androgen receptor (AR) antagonist selected for potent AR activity and devoid of partial agonist effects. A preliminary report of the phase I/II study described anti-tumor activity and adverse events (Scher HI et al. Lancet. 2010;375:1437). This abstract provides long-term follow-up on time to PSA and radiographic progression in this trial. Methods: Patients (pts) with progressive castration resistant prostate cancer (CRPC) were enrolled in sequential cohorts of 3-6 pts at MDV3100 doses of 30, 60, 150, 240, 360, 480 and 600 mg/day. Once the tolerability of a dose was established, enrollment was expanded at doses ≥60 mg/day to include approximately 12 chemotherapy naïve (naïve) pts and 12 pts previously treated with docetaxel (post-chemo) per cohort. Results: 140 pts were enrolled of which 18 (13%) pts continue on active treatment (16 naive and 2 post-chemo). The median time on treatment is 51 weeks for naïve and 17 weeks for post-chemo groups. Median time on treatment for the 18 patients still on study is 131 weeks. The median time to PSA progression, defined per-protocol as a ≥25% increase in PSA from baseline, was not met for naïve and was 33 weeks for post-chemo groups. Median time to PSA progression by Prostate Cancer Clinical Trials Working Group 2 criteria was 41 weeks for naïve and 20 weeks for post-chemo groups. Median time to radiographic progression was 56 weeks for naive and 24 weeks for post-chemo groups. Circulating tumor cell counts available for 128 of 140 pts showed 91% (70/77) with favorable pre-treatment counts (<5 cells/7.5 mL blood) remaining favorable post-treatment, while 49% (25/51) converted from unfavorable pre-treatment to favorable post-treatment. Conclusions: MDV3100 demonstrates durable anti-tumor activity in pts with CRPC both before and after chemotherapy. Based on these promising results MDV3100 is currently being evaluated in two global phase III studies in pts with metastatic CRPC, the AFFIRM study in pts previously treated with docetaxel and the PREVAIL study in chemotherapy-naïve pts who have progressed on androgen deprivation therapy. [Table: see text]

Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer

“…After longer follow-up, enzalutamide continued to demonstrate durable tumor responses 9. At the time of the updated analysis, 18 patients were still on study with a median time on treatment of 131 weeks.…”

Enzalutamide: A Novel Antiandrogen for Patients with Castrate-Resistant Prostate Cancer

“…Exploratory studies using 16b- [18F] fluoro-5a-dihydrotestosterone (FDHT) imaging and circulating tumor cells showed improvement posttreatment in subsets of patients, which correlated with clinical outcomes. Long-term follow-up data presented in 2011 showed median time to radiographic progression of 56 weeks in chemotherapy-na€ ve men and 24 weeks in men previously treated with chemotherapy (8).…”

Metastatic Castration-Resistant Prostate Cancer: Critical Review of Enzalutamide

“…Three patients developed seizures and those three patients were receiving the 360 mg dosage or higher, and two of the patients were on medications that lowered the seizure threshold. At longer follow-up and at the time of updated analysis, 18 of the enrolled patients remained in the study, with a median time on therapy of 131 weeks 28. The median time to PSA progression [as assessed by the Prostate Cancer Working Group 2 (PCWG2)]29 was 41 weeks and 20 weeks in the chemotherapy-naïve and the chemotherapy-pretreated groups, respectively.…”