Enzalutamide Improves HRQOL Over Placebo, Leuprolide

Results from the phase 3 EMBARK trial demonstrated the efficacy of enzalutamide plus leuprolide acetate and enzalutamide alone for the treatment of high-risk, biochemically recurrent (BCR), nonmetastatic castration-sensitive prostate cancer (nmCSPC). The combination resulted in significantly delayed metastasis-free survival (MFS) when compared with placebo plus leuprolide.

The primary analysis of the trial showed no significant differences in time to first and confirmed clinically meaningful deterioration between either treatment arm and placebo with leuprolide for pain progression and health-related quality of life (HRQOL). New results of the secondary objective concerning the change from baseline patient-reported outcomes (PRO) for pain and HRQOL were presented at the 24th Annual Meeting of the Society of Urologic Oncology by Dr. Stephen J. Freedland, of Cedars-Sinai. A restricted maximum-likelihood-based mixed model for repeated measures approach was used in a longitudinal analysis to determine change from baseline.

In the EMBARK trial, patients with high-risk BCR nmCSPC were randomized 1:1:1 to receive enzalutamide plus leuprolide, enzalutamide alone, or placebo plus leuprolide. PROs were assessed at baseline and every 12 weeks until metastasis or death. Deterioration was defined as a decrease of ≥10 points from baseline in the Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score and an increase of ≥2 points in the Brief Pain Inventory short form worst pain score.

Secondary analysis examined treatment differences up to week 205 in the intent-to-treat patient population. At baseline, all patients were asymptomatic and had good HRQOL; 327 to 332 patients from each group completed a PRO questionnaire. Completion rates after baseline and up to week 205 were  85% or greater. At week 205, no meaningful deterioration in pain progression was seen with any treatment. For worst pain, the differences between each treatment arm and placebo plus leuprolide were not statistically significant.

In the FACT-P total score, changes from baseline scores were significantly different in favor of placebo plus leuprolide but did not meet the measurement for clinically meaningful differences. No significant differences in change from baseline were observed in treatment arms for urinary symptoms and bowel symptoms or function.

Statistically significant differences were observed in sexual activity favoring enzalutamide alone, and in hormone treatment-related symptoms favoring placebo plus leuprolide. The 5-level EQ-5D visual analogue scale scores were stable across all treatment arms. After week 37, the HRQOL scores trended back toward baseline levels.

In each treatment arm, patients reported high HRQOL scores at baseline across multiple patient-reported surveys. No clinically significant differences in HRQOL were seen longitudinally up to week 205. For specific subdomains, the enzalutamide monotherapy arm saw the smallest deterioration in sexual activity, and the placebo-plus-leuprolide group experienced the smallest deterioration in hormone-related symptoms.

Enzalutamide plus leuprolide or enzalutamide monotherapy improve MFS over placebo plus leuprolide while maintaining HRQOL in patients with high-risk BCR nmCSPC.