The FDA approved the use of Xtandi® (enzalutamide) in men who have not yet received chemotherapy, significantly expanding the potential patient population eligible to be treated with the oral medicine.  Xtandi originally gained U.S. approval in 2012 for use in patients with castration-resistant prostate cancer that has spread beyond the prostate only after they had first received chemotherapy treatment.

The results of a study presented at the 2014 Genitourinary Cancers Symposium demonstrated that Xtandi improved survival and reduced the risk of radiographic progression in men with chemotherapy-naïve, metastatic, hormone-refractory prostate cancer.

The prostate is a male sex gland responsible for producing fluid that forms semen. It is located below the bladder, in front of the rectum, and surrounds the urethra. Prostate cancer occurs when the cells in the prostate gland grow out of control.

Prostate cancer is a hormonally sensitive disease that can often be controlled for long periods with androgen deprivation therapy (ADT). When prostate cancer stops responding to this treatment, it is referred to as hormone-refractory prostate cancer. Metastatic hormone-refractory prostate cancer is a challenging form of the disease to treat because the cancer has spread to distant sites in the body and does not respond to treatment with hormonal therapy.

Xtandi targets multiple steps in the androgen-receptor–signaling pathway, interfering with molecular pathways that help the cancer grow. What’s more, the drug does not cause side effects commonly associated with chemotherapy, such as nausea and hair loss.

The PREVAIL trial was a randomized, double-blind, placebo-controlled, multicenter phase III study that included 1,715 patients with asymptomatic or mildly symptomatic metastatic hormone-refractory prostate cancer who had not received previous chemotherapy. Patients were randomly assigned to Xtandi or placebo plus standard hormone therapy. The two primary endpoints were overall survival and radiographic progression-free survival.

The results indicated that Xtandi reduced the risk of death by 30 percent and reduced the risk of radiographic progression by 81 percent. Overall response rate was 59 percent with Xtandi (20% complete responses and 39% partial responses) compared with 5 percent in the placebo group. Estimated median overall survival was 32.4 months in the Xtandi group and 30.2 months in the placebo group. Xtandi delayed the need for chemotherapy by a median of 17 months: Median time to chemotherapy was 28 months in the Xtandi group compared with 10.8 months in the placebo. At the time of the analysis, 28 percent of Xtandi patients and 35 percent of placebo patients had died.

The researchers concluded that treatment with Xtandi significantly improves overall survival and radiographic progression-free survival in men with chemotherapy-naïve metastatic hormone-refractory prostate cancer. As a result of the data at interim analysis, an Independent Data Monitoring Committee recommended stopping the study and offering allowing placebo patients to receive Xtandi.


Beer TM, Armstrong AJ, Sternberg CN, et al: Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study. Presented at the 2014 Genitourinary Cancers Symposium. Journal of Clinical Oncology. 2014; 32 (supplement 4; abstract LBA1).

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