Enzalutamide with or without leuprolide also reduces the risk of prostate-specific antigen progression in those with non-metastatic hormone-sensitive prostate cancer in the phase 3 EMBARK trial.
Combination therapy with enzalutamide (Xtandi) and leuprolide produced a statistically significant improvement in metastasis-free survival (MFS) compared with placebo plus leuprolide in those with non-metastatic hormone-sensitive prostate cancer (HSPC) at high-risk of biochemical recurrence (BCR), according to a press release on data from the phase 3 EMBARK trial (NCT02319837).
Compared with placebo/leuprolide, enzalutamide/leuprolide reduced the risk of death or metastasis by 58% as assessed by MFS (Hazard ratio [HR], 0.42; 95% CI, 0.30-0.61; P <.0001). Additionally, the enzalutamide monotherapy arm also met the MFS end point vs the placebo arm (HR, 0.63; 95% CI, 0.46-0.87; P = .0049). Enzalutamide plus leuprolide and enzalutamide monotherapy, respectively, reduced the risk of prostate-specific antigen (PSA) progression by 93% (HR, 0.07; 95% CI, 0.03-0.14; P <.0001) and 67% (HR, 0.33; 95% CI, 0.23-0.49; P <.0001) vs placebo plus leuprolide.
The progression risk of initiating new antineoplastic therapy was reduced by 64% among those receiving enzalutamide plus leuprolide compared with placebo plus leuprolide (HR, 0.36; 95% CI, 0.26-0.49; P <.0001). Enzalutamide monotherapy reduced the progression risk of new antineoplastic therapy by 46% compared with placebo plus leuprolide (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).
There was a positive trend in the secondary end point of overall survival (OS) in the enzalutamide combination arm, although these data were immature. Investigators plan to follow up with patients for a final OS analysis.
Investigators plan to submit detailed data from the EMBARK trial for peer-reviewed publication and discuss them with regulatory authorities, including the FDA, to enable a potential regulatory submission for enzalutamide in non-metastatic HSPC in 2023.
“There are patients with localized prostate cancer who undergo prostatectomy or radiation therapy in an attempt to cure their disease, but, unfortunately, some patients will develop BCR,” lead study investigator Neal Shore, MD, FACS, U.S chief medical officer of Urology and Surgical Oncology at GenesisCare and director of the Carolina Urologic Research Center, said in the press release. “The clinical goal of BCR therapy is to delay cancer progression and avoid metastatic disease. The MFS results from the EMBARK study demonstrate that this intervention with [enzalutamide] plus leuprolide was statistically significant for patients with high-risk BCR.”
Investigators of the randomized, double-blind, placebo-controlled phase 3 EMBARK trial assessed 1068 patients who had non-metastatic HSPC with at high-risk of BCR at treatment sites across the United States, Canada, South America, and the Asia/Pacific region. Patients were randomly assigned to receive 160 mg of enzalutamide monotherapy (n = 355), 160 mg of enzalutamide daily plus 22.5 mg of leuprolide once every 12 weeks (n = 355), or placebo plus leuprolide (n = 358).
Secondary end points of the EMBARK trial included time to castration resistance, time to PSA progression, time to distant metastasis, and quality of life.
Patients 18 years and older with histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy were eligible for enrollment on the trial. Additional eligibility criteria included having prostate cancer initially treated with radical prostatectomy or radiotherapy, a PSA doubling time of 9 or fewer months, and a serum testosterone level of at least 150 ng/dL.
The overall safety profile observed in the EMBARK trial was consistent with the known safety profiles of each individual agent. Common adverse effects included fatigue, hot flush, and arthralgia in those receiving enzalutamide plus leuprolide as well as fatigue, gynecomastia, and arthralgia in patients receiving enzalutamide monotherapy.
Investigators presented data from the EMBARK trial at a plenary session during the 2023 American Urological Association’s Annual Meeting (AUA).
XTANDI® (enzalutamide) plus leuprolide reduced the risk of metastasis by 58% in non-metastatic hormone-sensitive prostate cancer versus placebo plus leuprolide. News release. Astellas Pharma Inc. April 29, 2023. Accessed May 1, 2023. bit.ly/41SHLjQ