Enzalutamide Shows Strong Activity in Prostate Cancer

Results from a phase III study show that the androgen-receptor blocker enzalutamide (Xtandi; Medivation and Astellas Pharma) increases survival by 29% in men with metastatic, castration-resistant prostate cancer and delays progression of the disease by 81%.

“Enzalutamide is likely to become an important new treatment option that has a significant impact on the progression of prostate cancer,” said lead author Tomasz Beer, MD, professor of medicine and deputy director of the Knight Cancer Institute at Oregon Health and Science University in Portland, who presented the data at the Genitourinary Cancers Symposium on January 30 in San Francisco, CA.

Researchers enrolled 1,717 men with metastatic, castration-resistant prostate cancer who had not previously received chemotherapy and randomly assigned them to receive enzalutamide or a placebo plus standard hormone therapy. The participants had previously received treatment, such as surgery or radiation therapy, for their disease, as well as hormone therapy or a first-generation antiandrogen, such as flutamide.

The two primary endpoints were overall survival and radiographic progression-free survival (PFS). Radiographic PFS uses routine bone and CT scans to monitor for cancer growth.

The results showed that enzalutamide slowed or stopped cancer growth in 59% of patients, compared with 5% of patients in the placebo arm. In addition, it significantly delayed the need for chemotherapy. On average, patients receiving enzalutamide needed chemotherapy 17 months later than those in the placebo arm (28 months vs. 10.8 months).

Based on this positive interim data, the data safety monitoring committee recommended that the trial be stopped in October 2013; trial participants who were receiving the placebo were offered enzalutamide. Although preliminary results were released at that time, full data were not available prior to Beer's presentation.

The most common side effects of enzalutamide included fatigue, constipation, and back and joint pain, in addition to side effects associated with other hormone therapies, such as weight gain and hot flashes. Overall, enzalutamide was well tolerated, with 6% of patients in each arm discontinuing therapy due to side effects.

Enzalutamide was approved by the U.S. Food and Drug Administration (FDA) in 2012 to treat prostate cancer in patients who have already received chemotherapy. Based on the new study results, partners Medivation and Astellas Pharma plan to seek FDA approval to expand the indication.

“This is a very important study from the perspective of patients who have not had chemotherapy,” said Charles J. Ryan, MD, who moderated the press conference at which the data was revealed. These patients, he said, currently have only one or two treatment options, such as chemotherapy.

“If approved for this indication, it will become an important standard option for use before chemotherapy in patients with asymptomatic or minimally symptomatic advanced prostate cancer,” agreed Beer.