Phase 3 Study Results Show Xtandi Plus Leuprolide Significantly Improves nmHSPC

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Enzalutamide (Xtandi), from Pfizer Inc and Astellas Pharma Inc, in combination with AbbVie’s leuprolide demonstrated clinically meaningful and statistically significant improvements in metastasis-free survival (MFS) for men with non-metastatic hormone-sensitive prostate cancer (nmHSPC), also known as non-metastatic castration-sensitive prostate cancer, according to positive topline results of the EMBARK trial (NCT02319837).

Individuals in the trial were randomized to 1 of 3 study arms: enzalutamide 160 mg as a monotherapy, enzalutamide 160 mg daily plus leuprolide, or a placebo plus leuprolide.

“As the only novel hormone therapy approved for 3 disease states of prostate cancer in the US, [enzalutamide] has impacted hundreds of thousands of men,” Chris Boshoff, MD, PhD, chief development officer of oncology and rare disease at Pfizer Global Product Development, said in a statement. “The topline findings from EMBARK are highly encouraging, and we look forward to engaging with health authorities to potentially bring [enzalutamide] to men with [nmHSPC] with high-risk biochemical recurrence.”

The EMBARK trialenrolled1068 individuals with nmHSPC with high-risk biochemical recurrence (BCR) at sites in the Asia-Pacific Region, Canada, Europe, South America, and the United States. Individuals were considered high-risk BCR if they had prostate-specific antigen (PSA) doubling time of 9 months or less, serum testosterone of 150ng/dL or more, screening PSA of 1 ng/mL or more, and had a radical prostatectomy, with or without radiotherapy, as a primary treatment for prostate cancer, or at least 2 ng/mL above the nadir if they had radiotherapy only as a primary treatment for prostate cancer.

At the time of the analysis, investigators reported that there was also a positive trend in the key secondary endpoint of overall survival (OS), but the data were not finalized. Individuals in the trial will be followed up for a subsequent final OS analysis.

Additionally, investigators reported that the study met the key secondary endpoint with a clinically meaningful and statistically significant improvement in MFS for individuals who were treated with the monotherapy compared with the placebo plus leuprolide, and time PSA progression and time to first use of new antineoplastic therapy were statistically significant.

Other key secondary endpoints are being analyzed, according to the statement.

No new safety signals were observed in the preliminary safety analysis, which remains consistent with the established safety profile, according to investigators.

“While current treatment options for localized prostate cancer are intended to be curative, some men remain at higher risk for biochemical recurrence following primary treatment, which may result in metastases,” Ahsan Arozullah, MD, MPH, senior vice president and head of development therapeutic areas at Astellas, said in the statement. “The EMBARK trial is the first study to demonstrate a statistically significant improvement in MFS using the combination of enzalutamide plus leuprolide in men with this stage of disease.”

Detailed results from the EMBARK trial will be presented at a future medical meeting.

The data will also be discussed with regulatory authorities, including the FDA, to support a potential regulatory submission for the drug in this indication.

Reference

Phase 3 study shows Xtandi (enzalutamide) plus leuprolide significantly improves metastasis-free survival in men with non-metastatic prostate cancer. Pfizer. News release. March 16, 2023. Accessed March 20, 2023. https://www.pfizer.com/news/press-release/press-release-detail/phase-3-study-shows-xtandir-enzalutamide-plus-leuprolide