The European Commission (EC) has approved a new indication for enzalutamide for the treatment of adult men with high-risk, non-metastatic, castration-resistant prostate cancer (nmCRPC).

This makes it one of the first treatments approved for this critical stage of disease, currently associated with a significant unmet medical need.

Enzalutamide was first approved by the EC in June 2013 and is already indicated in the treatment of adult men with metastatic CRPC who are asymptomatic, or mildly symptomatic after failure of androgen deprivation therapy (ADT), in whom chemotherapy is not yet clinically indicated, or whose disease has progressed on, or after docetaxel therapy.

The approval is based on the results from the pivotal phase 3 PROSPER trial which evaluated enzalutamide plus ADT vs. placebo plus ADT in patients with nmCRPC and rapidly rising prostate-specific antigen (PSA) levels, as defined by a PSA doubling time of 10 months or less and a PSA level of ≥ 2ng/ml.

“This new approval is important progress for men with CRPC, who now have enzalutamide as a treatment option regardless of whether or not they have detectable metastatic disease,” said Bernhardt G. Zeiher, M.D., Chief Medical Officer, Astellas. “We are committed to working with health authorities across Europe to ensure that enzalutamide is made available as soon as possible to men with high-risk nmCRPC.”

The EC marketing authorisation for enzalutamide is applicable to the 28 European Union (EU) member countries plus Iceland, Norway and Liechtenstein.

The PROSPER trial

PROSPER is a double-blind, placebo-controlled, pivotal phase 3 trial conducted at 300 sites in 32 countries that randomised 1,401 patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and a prostate-specific antigen (PSA) doubling time of 10 months or less.

Participants received either once-daily enzalutamide plus androgen deprivation therapy (ADT) (n=933) or placebo plus ADT (n=468) (2:1), respectively.

The results of this study were published in the New England Journal of Medicine.

The trial met its primary endpoint of metastasis-free survival (MFS).

The median MFS was 36.6 months for men who received enzalutamide plus ADT, compared to 14.7 months with placebo plus ADT (n=1401; HR=0.29 [95% CI: 0.24–0.35]; p<0.001).

The results from this trial indicated a 71 percent reduction in the risk of metastasis or death in men with nmCRPC and rapidly rising PSA levels, compared to placebo plus ADT (HR=0.29 [95% CI: 0.24–0.35]; p<0.001).

Secondary outcomes included a statistically significant delay in the median time to first use of new antineoplastic therapy of 39.6 vs.17.7 months; HR=0.21 [95% CI: 0.17–0.26]; p<0.001 for patients who received enzalutamide plus ADT compared to those who received placebo plus ADT.

The most common adverse events of any grade for patients ≥10 percent and higher for enzalutamide plus ADT vs. placebo plus ADT were: fatigue (33 percent vs. 14 percent), hot flush (13 percent vs. 8 percent), hypertension (12 percent vs. 5 percent), nausea (11 percent vs. 9 percent), fall (11 percent vs. 4 percent), dizziness (10 percent vs. 4 percent) and decreased appetite (10 percent vs. 4 percent).

Source: Astellas