Enzalutamide Before Chemotherapy for Prostate Cancer

Summary and Comment |
June 10, 2014

Enzalutamide Before Chemotherapy for Prostate Cancer

  1. Robert Dreicer, MD, MS, FACP

This oral androgen-receptor inhibitor reduced risk for radiographic progression and death.

  1. Robert Dreicer, MD, MS, FACP

Although testosterone-suppressive therapy has been the standard of care for initial management of metastatic prostate cancer for more than 7 decades, recent progress in understanding the disease at the molecular level provides compelling evidence that the androgen receptor remains the primary driver of the disease throughout the entire disease course. Next-generation androgen pathway inhibitors such as abiraterone and enzalutamide have received FDA approval by demonstrating survival benefit in patients with advanced prostate cancer following docetaxel chemotherapy.

Now, to test the utility of enzalutamide in metastatic castration-resistant prostate cancer prior to chemotherapy, investigators conducted an industry-sponsored, international, phase III, randomized, double-blind, placebo-controlled trial involving 1717 patients. Primary endpoints were radiographic progression-free survival (PFS) and overall survival.

Treatment with enzalutamide was longer than with placebo (median 16.6 vs. 4.6 months), and at 12-month follow-up, it resulted in superior radiographic PFS (65% vs. 14%; 81% risk reduction; hazard ratio, 0.19; P=0.001) and a 29% reduction in risk for death (HR, 0.79; P=0.001). Enzalutamide was well tolerated; the most common clinically relevant adverse events were fatigue and hypertension.


The data from this large study is currently under review at the FDA, where a broadening of the indication of enzalutamide is likely to be recommended. If approved, enzalutamide would be available for use in this earlier clinical setting along with abiraterone. Cross resistance to these agents used in sequence is increasingly recognized, and the optimal sequence remains undefined. Ongoing clinical trials may provide additional information regarding sequence and the role of combination therapy.

Editor Disclosures at Time of Publication

  • Disclosures for Robert Dreicer, MD, MS, FACP at time of publication Consultant / Advisory board Millenium; Dendreon; Medivation; Janssen; Roche Speaker's bureau Bayer Editorial boards Urology; Clinical Genitourinary Cancer; Current Urology Reports Leadership positions in professional societies National Cancer Institute (Co-Chair, GU Oncology Steering Committee)


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