Enzalutamide Monotherapy Highly Active in Patients with Prostate Cancer Who Have Had No Prior Hormone Therapy 

Get Permission

©ASCO/Todd Buchanan 2013

Enzalutamide (Xtandi) monotherapy induced striking declines in prostate-specific antigen (PSA) in a majority of patients with hormone-naive prostate cancer in a phase II trial, and this oral agent appears to have little effect on bone mineral density. If these findings are confirmed in a phase III trial, then enzalutamide may be an alternative to androgen deprivation therapy in recurrent and metastatic prostate cancer with fewer side effects.

Effective Monotherapy

“Enzalutamide achieved marked PSA responses and PSA declines in men with hormone-naive prostate cancer. We believe the results of this trial compare favorably with [the data for androgen deprivation therapy]. In contrast with [androgen deprivation therapy], patients treated with enzalutamide had stable bone mineral density and only modest changes in serum triglycerides. The beneficial effects seen in this phase II trial are consistent with those seen with potent [androgen deprivation therapy] inhibition, and support the role of enzalutamide as monotherapy in prostate cancer,” reported Matthew R. Smith, MD, PhD, of Massachusetts General Hospital in Boston.

Although androgen deprivation therapy is considered the mainstay of treatment for recurrent or metastatic prostate cancer, the side effects can be difficult for men to tolerate. These include hot flashes, fatigue, loss of libido and erectile function, increased risk of bone mineral density loss, decreased muscle mass, and decreased insulin sensitivity that increases the risk of diabetes and cardiovascular disease. Bicalutamide was evaluated as an alternative to androgen deprivation therapy, and although the drug seems to have little or no effect on bone mineral density, it also appears to be less effective than standard androgen deprivation therapy, Dr. Smith said.

“Hormone therapy with a high level of efficacy and fewer adverse events [than androgen deprivation therapy] is an unmet medical need. Enzalutamide is a novel oral androgen receptor inhibitor approved by the FDA for treatment of men with castration-resistant prostate cancer and disease progression after docetaxel therapy. It makes sense to study this drug earlier in the course of disease,” he continued.

Study Details

The phase II open-label, multicenter study evaluated enzalutamide as monotherapy in patients with hormone-naive prostate cancer for which androgen deprivation therapy is indicated. All patients had testosterone levels ≥ 230 ng/mL, PSA ≥ 2 ng/mL, and life expectancy of at least 12 months.

Patients were treated with enzalutamide monotherapy for 25 weeks. At that point, a primary efficacy analysis was performed. Patients deemed eligible could continue on therapy. The study included 67 men, with a median age of 73 years, mean body mass index of 22.6 kg/m2, median baseline PSA of 18.2 ng/mL, and median duration of prostate cancer since diagnosis of 1 year; 50% had Gleason 7 scores and 25% had Gleason 8 to 10 scores at entry. Approximately 38% had metastasis at study entry, and about one-third had had a prior prostatectomy.

The primary endpoint was PSA response (at least an 80% decline in PSA level). Monotherapy with enzalutamide achieved marked and rapid PSA declines in 92.5% of patients. Median PSA decrease was –99.6%. A total of 62 of 67 (92.5%) achieved the primary endpoint of PSA decline > 80% at week 25, including patients with and without metastasis at baseline. Four of five patients categorized as nonresponders were actually patients who withdrew from the study before response was evaluable.

Among 16 patients evaluable for objective responses with measurable disease, the complete plus partial response rate was 50%. Dr. Smith said that the data on durability of response will be included in the full publication of the trial’s results, but he did not have those data at the time of the Annual Meeting.

Adverse Effects

The expected rate of decline in bone mineral density is 3% to 5% during the first year of androgen deprivation therapy. In this study, no significant changes in bone mineral density were observed after 25 weeks of treatment with enzalutamide. In fact, bone mineral density increased at the femoral neck by about 0.4%.

After 25 weeks of enzalutamide monotherapy, mean body mass index decreased by 4.2%, and body fat increased by 6.9%. Moderate increases were seen in serum triglycerides (6.5%) and total cholesterol levels (+4.6%), and these changes compare favorably with the effect of androgen deprivation therapy on these parameters. ■

Disclosure: Dr. Smith has served in a consultant or advisory role for Astellas Pharma and has received honoraria from Medivation.


1. Smith MR, Borre M, Rathenborg P, et al: Efficacy and safety of enzalutamide monotherapy in hormone-naive prostate cancer. 2013 ASCO Annual Meeting. Abstract 5001. Presented June 3, 2013.

Related Articles

Expert Point of View: Michael A. Carducci, MD

With the high rate of [prostate-specific antigen (PSA)] decline, the study of enzalutamide ­(Xtandi) reported by Dr. Smith and colleagues appears to be a positive study,” said formal discussant ­Michael A. ­Carducci, MD, AEGON Professor in Prostate Cancer Research at the Sidney Kimmel Comprehensive ...