Enzalutamide for Hormone-Naïve Prostate Cancer

Chicago—Patients with hormone-naïve prostate cancer who took 160 mg of enzalutamide daily for 24 weeks had a median decrease in prostate-specific antigen (PSA) of 99.6%, according to a phase 2, open-label, single-arm study. In addition, 92.5% of patients had a PSA response, which was defined as a ≥80% decline in PSA after treatment.

Matthew R. Smith, MD, PhD, the study’s lead author, presented the data during a clinical science symposium at the ASCO meeting. Astellas Pharma US, Inc. and Medivation, Inc., the drug’s marketers, supported the study.

“These post-treatment PSA changes were rapid, with near maximal decline for the population seen by 10 weeks,” Dr. Smith said.

The FDA approved enzalutamide, an oral androgen receptor inhibitor, in August 2012 to treat men with metastatic castration-resistant prostate cancer who previously had received treatment with docetaxel. The approval was based on results of a phase 3 trial that found patients who took enzalutamide had an increased median overall survival of 4.8 months compared with a placebo group.

For recurrent or metastatic prostate cancer, Dr. Smith noted that androgen deprivation therapy, either through medical or surgical castration, is the standard treatment option. Although it is an effective method, it is also associated with side effects, including hot flashes, fatigue, and loss of sexual interest. Androgen deprivation therapy also decreases bone mineral density, insulin sensitivity, and muscle mass and increases the risk for clinical fractures as well as cholesterol and triglycerides.

An alternative to androgen deprivation therapy is bicalutamide, an oral drug that Dr. Smith said has some quality-of-life advantages and an improved safety profile. However, he added that randomized trials have indicated bicalutamide monotherapy is less effective than androgen deprivation therapy.

In the current study, the authors enrolled 67 patients with histologically confirmed prostate cancer who would otherwise have received standard androgen deprivation therapy. Each man had noncastrate testosterone levels ≥230 ng/dL, PSA ≥2 ng/mL, an Eastern Cooperative Oncology Group performance status score of 0 at baseline, and life expectancy ≥12 months. If a patient had clinical benefit after 24 weeks of treatment, he could continue until disease progression or toxicity. The authors performed a safety follow-up for 30 days after the last dose.

The median age of patients was 73 years, median body mass index was 26.2 kg/m², median PSA was 18.2 ng/mL, and median duration of prostate cancer was 1.0 years.

Of the 67 patients, 62 achieved the primary end point of a ≥80% decline in PSA after treatment with enzalutamide. Of the 5 other patients, 4 were classified as nonresponders because they withdrew from the study before the assessment.

Dr. Smith mentioned that PSA decline was similar in patients with and without metastatic disease at baseline. In addition, 16 patients were measured for objective responses of measurable disease after the 24-week treatment period: 3 had a complete response, 5 had a partial response, 3 had stable disease, 3 had progressive disease, and 2 had neither complete response nor progressive disease.

“We believe these results compare favorably with that expected with standard androgen deprivation therapy,” Dr. Smith said.

In addition, 89.6% of patients had an adverse event, 79.1% had a drug-related adverse event, and 7.5% had a serious adverse event. There were no drug-related serious adverse events. The following treatment-emergent adverse events were found in at least 10% of patients: gynecomastia, fatigue, nipple pain, hot flashes, diarrhea, and nausea. All of the common adverse events were grade 1 or 2.

Whereas androgen deprivation therapy decreases bone mineral density by an average of 3% to 5% in the first year, this study found that patients taking enzalutamide had no significant change in bone mineral density during the treatment period, according to Dr. Smith.