Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer post docetaxel Results from the phase III AFFIRM study

SUMMARY: MDV3100 is an androgen receptor antagonist with a significantly higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide and there by competitively inhibits the binding of androgens to the androgen receptor. Majority of the patients with advanced prostate cancer become refractory to hormone therapy because of increased production of androgen receptors by the tumors as well as mutated androgen receptors. The superiority of this novel agent, MDV3100, is based on the fact that the expression of androgen dependent genes are downregulated with MDV 3100 leading to cell death or apoptosis, whereas with bicalutamide the expression of these genes are upregulated. Further MDV3100 continues to antagonize mutated androgen receptors on the prostate tumor cells in contrast to bicalutamide which behaves as an agonist. It is thus an androgen receptor signaling inhibitor (ARSI). The AFFIRM clinical trial is a randomized, multinational phase III study in which patients who had received prior docetaxel-based chemotherapy regimens were randomized 2:1 to receive either MDV3100, 160 mg/day or placebo. Patients treated with MDV3100 had a median survival of 18.4 months, compared with 13.6 months for men treated with placebo, with a median OS advantage of 4.8 months and a reduction in the risk of death by 37%. Scher HI, Fizazi K, Saad F, et al. J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)