Enzalutamide Combo Receives FDA Approval for Non-Metastatic CSPC

Enzalutamide plus leuprolide was assessed as part of the phase 3 EMARK study in patients with non-metastatic castration-sensitive prostate cancer at high risk of biochemical recurrence.

Enzalutamide (Xtandi) has been approved by the FDA for patients with non-metastatic castration-sensitive prostate cancer at high risk of biochemical recurrence, according to a press release from the agency.¹

Experts noted that patients may receive enzalutamide with or without a gonadotropin-releasing hormone analog therapy, such as leuprolide as was analyzed in the study.

“For patients who were previously treated for prostate cancer and had achieved remission, only to later receive the distressing news of disease recurrence with a risk of metastasis, the emotional toll can be profound,” Courtney Bugler, president and chief executive officer of ZERO Prostate Cancer, said in the press release. “This approval of [enzalutamide] is a promising treatment option for the community, offering a ray of hope to patients and their caregivers during these challenging times.”

Results from the phase 3 EMBARK study (NCT02319837) supported the approval, with investigators reporting a reduction in recurrence or risk of death of 58% among patients treated with the combination (HR, 0.42; 95% CI, 0.30-0.61; P <.0001).²

A total of 1068 patients were enrolled and received either 160 mg of enzalutamide plus leuprolide (n = 355), 160 mg of enzalutamide (n = 355), or placebo plus leuprolide (n = 358). The study’s primary end point was metastasis-free survival and secondary end points were time to castration resistance, time to prostate-specific antigen (PSA) progression, time to distant metastasis, and quality of life.

The risk of PSA progression was reduced by 93% (HR, 0.07; 95% CI, 0.03-0.14; P <.0001) in the combination arm vs 67% (HR, 0.33; 95% CI, 0.23-0.49; P <.0001) in the placebo arm.

When new antineoplastic therapy was initiated, the progression risk was reduced by 64% in the combination group vs the placebo group (HR, 0.36; 95% CI, 0.26-0.49; P <.0001). For enzalutamide monotherapy, there was a reduction of progression risk for new antineoplastic therapy by 46% vs the placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).

The safety profile remained consistent with other known safety profiles for each agent individually. The most common adverse effects reported included fatigue, hot flush, and arthralgia in the combination arm and fatigue, gynecomastia, and arthralgia in patients receiving enzalutamide monotherapy in the monotherapy arm.

To be included in the study, patients must have histologically or cytologically confirmed adenocarcinoma of the prostate during the initial biopsy, have prostate cancer that was initially treated by radical prostatectomy or radiotherapy, and a PSA doubling time of 9 months or less. Patients must also have a screening of PSA by central biopsy by the central laboratory of 1 ng/mL or more for radical prostatectomy and 2 ng/mL for radiotherapy.

Patients were excluded if they had prior evidence of distant metastatic disease, prior hormonal therapy, and prior cytotoxic chemotherapy aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer.

References

1. Pfizer and Astellas’ Xtandi approved by U.S. FDA in earlier prostate cancer setting. News release. Astellas. November 17, 2023. Accessed November 17, 2023. https://shorturl.at/KRV46
2. 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 November 13, 2023. bit.ly/41SHLjQ