XTANDI® (Enzalutamide) now approved for Late-Stage Prostate Cancer

SUMMARY:The US Food and Drug Administration (FDA) approved XTANDI® (Enzalutamide), an oral agent, formerly known as MDV3100, for men with metastatic castration-resistant prostate cancer who had progressed on TAXOTERE® (Docetaxel) based chemotherapy regimen. The approval was based on the results from the AFFIRM clinical trial. XTANDI® 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, XTANDI®, is based on the fact that the expression of androgen receptor dependent genes are downregulated with XTANDI® leading to cell death or apoptosis, whereas with bicalutamide the expression of these genes are upregulated. Further XTANDI® 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 XTANDI®, 160 mg/day or placebo. Patients treated with XTANDI® 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)