Xtandi Gains Approval for Nonmetastatic Castration-Sensitive Prostate Cancer

The Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Xtandi^® (enzalutamide) for the treatment of patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR). 

The approval was based on data from the phase 3 EMBARK trial (ClinicalTrials.gov Identifier: NCT02319837), which enrolled 1068 patients with nmCSPC with high-risk BCR. Study participants were randomly assigned to receive either enzalutamide plus leuprolide (n=355), placebo plus leuprolide (n=358), or enzalutamide monotherapy (n=355). The primary endpoint was metastasis-free survival (MFS) compared between the enzalutamide plus leuprolide and placebo plus leuprolide arms.

Findings showed enzalutamide plus leuprolide significantly reduced the risk of metastasis or death by 58% vs placebo plus leuprolide (hazard ratio [HR]: 0.42 [95% CI, 0.30-0.61]; P <.0001). A statistically significant improvement in MFS was also demonstrated in patients who received enzalutamide monotherapy compared with those who received placebo plus leuprolide (HR, 0.63 [95% CI, 0.46-0.87]; P =.0049). At the time of analysis, overall survival data were not mature; 12.2% of patients died in the overall population. 

There were no new safety signals observed in the study. The most common adverse reactions with Xtandi treatment include musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache.

“Previously, treatment options for these BCR patients, especially those who have a high likelihood of developing metastases were limited,” said Neal Shore, MD, FACS, Chief Medical Officer of Strategic Innovation and Pharmacy, GenesisCare USA, Director, CPI, Carolina Urologic Research Center, and primary investigator for the EMBARK trial. “The FDA approval of Xtandi for patients with nmCSPC with BCR at high risk of metastasis represents an important advancement whereby an androgen deprivation signaling inhibitor, enzalutamide, has achieved standard of care discussion for patient-physician decision-making.” 

Xtandi is also approved for the treatment of patients with castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer.