Enzalutamide, an androgen receptor inhibitor, delays metastasis in men with non-metastatic, castration-resistant prostate cancer (CRPC) and a rapidly rising PSA level, according to new study findings published online in the New England Journal of Medicine.

In the double-blind, phase 3 PROSPER trial (NCT02003924), Maha Hussain, MD, of Northwestern University in Chicago, and colleagues randomly assigned 1401 patients with a PSA doubling time of 10 months or less (median 3.7 months) on androgen deprivation therapy (ADT) to enzalutamide (160 mg) or placebo once daily. Over 3 years, nearly a quarter of enzalutamide-treated patients and half of placebo recipients developed metastasis or died.

Investigators found that enzalutamide prolonged metastasis-free survival by almost 2 years compared with placebo (36.6 vs 14.7 months). Patients who received enzalutamide had a significant 71% lower risk for metastasis or death. In addition, enzalutamide significantly delayed subsequent antineoplastic therapy and PSA progression, with no decrease in quality of life.

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Grade 3 or higher events occurred in 31% and 23% of the enzalutamide and placebo groups, respectively. Greater proportions of enzalutamide recipients experienced fatigue, hypertension, cardiovascular events, mental impairment, falls, and fractures.

In an accompanying editorial, Matthew R. Smith, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, said the FDA approval of apalutamide—the first drug the agency approved for treating non-metastatic CRPC—“and the anticipated approval of enzalutamide in the same context represent important steps forward for men with rising PSA levels during androgen deprivation therapy. The benefit–risk evaluation suggests that treatment with either drug is better than waiting until the appearance of metastases.”

The study was funded by Pfizer and Astellas Pharma, the makers of enzalutamide (Xtandi).

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Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2018;378:2465-74. DOI: 10.1056/NEJMoa1800536 [Published online June 28, 2018]

Smith MR. Progress in nonmetastatic prostate cancer. N Engl J Med 2018;378:26. DOI: 10.1056/NEJMe1805733