The phase 3 EMBARK trial demonstrated that combining enzalutamide with leuprolide significantly improves overall survival in patients with biochemically recurrent prostate cancer, showing a 40.3% reduction in the risk of death.

The trial involved 1,068 high-risk BCR patients across multiple regions, characterized by PSA doubling time of 9 months or less, serum testosterone of at least 150 ng/dL, and specific PSA thresholds.

An 8-year overall survival rate of 78.9% was observed in patients receiving the combination therapy, compared to 69.5% with leuprolide alone, with a median follow-up of approximately 94 months.

The safety profile of XTANDI remained stable, with common adverse events including hot flashes, fatigue, gynecomastia, and hypertension.

While XTANDI as monotherapy showed a numerical improvement over leuprolide alone, it did not reach statistical significance.

These findings support early intervention with enzalutamide in high-risk biochemical recurrence, especially since up to 90% of men with high-risk BCR develop metastatic disease and about one-third die from metastatic prostate cancer.

Enzalutamide monotherapy showed a 17% reduction in the risk of death versus leuprolide, but this result was not statistically significant.

These results reinforce previous findings that enzalutamide, either alone or with leuprolide, improves metastasis-free survival, leading to FDA approval of enzalutamide for high-risk non-metastatic castration-sensitive prostate cancer in November 2023.

The combination therapy extended time to first use of additional antineoplastic treatments, delayed skeletal events, and prolonged progression-free survival on subsequent therapies, with secondary endpoints showing significant delays in PSA progression and symptomatic skeletal events.

Across all patient subgroups, every subset benefited from adding enzalutamide to androgen deprivation therapy, indicating broad efficacy.

The safety profile remained consistent with previous analyses, with no new safety signals and serious adverse events below 10%, supporting the tolerability of the combination.

XTANDI is approved in over 80 countries for various prostate cancer indications, with over 1.5 million patients treated globally.