Nonsteroidal antiandrogen therapy with or without androgen deprivation therapy

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

After a follow-up of 60.7 months, the enzalutamide-leuprolide combination was superior to leuprolide monotherapy for the primary end point of 5-year metastasis-free survival (87.3% vs. 71.4%; HR, 0.42; 95% CI, 0.30–0.61; P < .001). After a follow-up of 60.7 months, enzalutamide monotherapy was superior to leuprolide monotherapy for a key secondary end point of 5-year metastasis-free survival (80.0% vs. 71.4%; HR, 0.63; 95% CI, 0.46–0.87; P < .005).[20][Level of evidence B1]

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

OS data were not mature, but at the time of the report, 12% of deaths were in the overall population, 3.4% were in the enzalutamide-leuprolide combination group, 6.1% were in the leuprolide monotherapy group, and 5.4% were in the enzalutamide monotherapy group.

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

Treatment suspension in all arms occurred at 36 weeks if PSA reached undetectable levels (<0.2 ng/mL). Treatment could be restarted per assigned treatment arms when the PSA increased to >2.0 ng/mL for patients who had a prior prostatectomy, or >5.0 ng/mL for patients who had prior primary radiation therapy. In the enzalutamide-leuprolide combination group, 90.9% of patients had treatment suspended for a median of 20.2 months. In the leuprolide monotherapy arm, 67.8% of patients had treatment suspended for a median of 16.8 months. In the enzalutamide monotherapy arm, 85.9% of patients had treatment suspended for a median of 11.1 months.

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

There was no substantial between-group differences in QOL measures.

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

No new safety signals were reported.

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

Grade 3 or higher toxicities for any adverse event were 46.5% in the enzalutamide-leuprolide combination group, 42.7% in the leuprolide monotherapy group, and 50.0% in the enzalutamide monotherapy group.

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

The most common adverse events in the combination group and leuprolide monotherapy group were hot flashes and fatigue. The most common adverse events in the enzalutamide monotherapy group were gynecomastia, hot flashes, and fatigue.

The phase III EMBARK trial (NCT02319837) included 1,068 men. Patients had received prior definitive therapy with radical prostatectomy and/or radiation therapy with curative intent, had a rapidly rising PSA, and were not candidates for salvage pelvic-directed therapy. Patients were randomly assigned in a 1:1:1 ratio to receive blinded enzalutamide (160 mg PO qd) with leuprolide, blinded placebo (PO qd) plus leuprolide, or open-label single-agent enzalutamide (160 mg PO qd).[20]

Adverse events of special interest included fractures, cognitive and memory impairment, and seizures. Fractures occurred in 18.4% of patients in the combination group, 13.6% of patients in the leuprolide monotherapy group, and 11% of the patients in the enzalutamide monotherapy group. Cognitive and memory impairment occurred in 15% of patients in the combination group, 6.5% of patients in the leuprolide monotherapy group, and 14.1% of patients in the enzalutamide monotherapy group. Seizures occurred in 1.1% of patients in the combination group, 0% of patients in the leuprolide monotherapy group, and 0.8% of patients in the enzalutamide monotherapy group.