The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion to expand the indication for enzalutamide to include adult men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC).

If approved by the European Commission (EC), enzalutamide will be 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 currently 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.

“In nmCRPC, the high risk patient is at a stage where his cancer is growing even though it’s not visible yet despite hormone therapy and will manifest itself given time. The objective of early access to enzalutamide in these patients is to delay the emergence of metastasis with the hope of improving quantity and quality of life” said Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, United States, and lead study investigator. “The potential of an effective treatment option for this stage of disease signifies an important therapeutic advancement.”

The CHMP opinion 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.

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 PROSPER trial results indicated a 71% reduction in the risk of radiographic progression 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).

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

These results were published in the June 2018 edition of the New England Journal of Medicine.

“This positive CHMP opinion represents an important step towards providing specialist health care professionals with a new treatment option for patients with nmCRPC and rapidly rising levels of prostate specific antigen. These patients are at higher risk of developing metastasis and death. Subject to EMA approval, we have the potential to expand the use of enzalutamide in a patient population where there is a clear unmet medical need” said Steven Benner, M.D, Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas.

The positive opinion from the CHMP will now be reviewed by the EC, which has the authority to approve medicines for the 28 European Union member countries plus Iceland, Norway and Liechtenstein.

The EC, which generally follows the recommendation of the CHMP, is expected to make its final decision in the final quarter of 2018.

Source: Astellas