Updated Results from the PREVAIL Trial: Efficacy of Enzalutamide on Visceral Metastases

Conference Correspondent - ESMO 2014 - Prostate Cancer

In the PREVAIL trial, enzalutamide significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared with placebo in chemotherapy-naïve men with metastatic castrate-resistant prostate cancer (mCRPC; Beer TM, et al. N Engl J Med. 2014;371:424-433).

Because patients with visceral metastases have a worse prognosis, this new post-hoc analysis of the PREVAIL trial presented at ESMO 2014 (Higano C, et al. ESMO 2014: Abstract 767P) described the outcomes from patients with baseline visceral disease (liver or lung metastases). In the PREVAIL trial, a total of 1717 men with mCRPC were randomized to receive enzalutamide or placebo, including 204 (11.9%) patients with visceral disease at screening (139 patients with lung disease, 74 with liver disease, and 9 patients with both). The men with visceral disease tended to have higher baseline median prostate-specific antigen (PSA) values (72.5 ng/mL vs 46.8 ng/mL), worse performance status (38.2% vs 31.1%, with ECOG = 1), and higher rates of lymph node disease (57.8% vs 49.8%) than those without visceral disease; however, both groups had similar rates of bone disease (80.4% and 83.7%, respectively).

As shown in the Table, compared with placebo, treatment with enzalutamide significantly improved median rPFS and time to PSA progression, as well as numerically improved median OS in the patients with visceral disease. Moreover, a significantly greater percentage of enzalutamide-treated patients with liver or with lung metastases achieved complete or partial response compared with the placebo group (Table).

The response rates tended to be higher in patients with lung metastases compared with patients with liver disease. The investigators concluded that enzalutamide is active in patients with mCRPC and visceral metastases, and this study supports the use of androgen receptor signaling as an important target in this patient population.