Enzalutamide Improves Survival in Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer
Enzalutamide (Xtandi) improved survival by 29% in men with chemotherapy-naive metastatic castration-resistant prostate cancer and reduced the risk of radiographic progression by 81%, according to complete results of the randomized, double-blind, placebo-controlled, multinational, phase III PREVAIL trial. These findings were presented at a press briefing in advance of the 2014 Genitourinary Cancers Symposium in San Francisco (Abstract LBA1).
“It is my view that enzalutamide provides a meaningful clinical benefit for men with metastatic castration-resistant prostate cancer. Enzalutamide is likely to become an important new treatment option that has a significant impact on the progression of prostate cancer. If it is approved in metastatic castration-resistant prostate cancer not previously treated with docetaxel or other chemotherapy, it will become an important standard option for use in patients with asymptomatic or minimally symptomatic advanced prostate cancer,” said lead author Tomasz Beer, MD, FACP, Deputy Director of the Knight Cancer Institute at Oregon Health & Science University, Portland.
Enzalutamide is a second-generation androgen-receptor blocker approved by the U.S. Food and Drug Administration for metastatic castration-resistant prostate cancer previously treated with docetaxel. It has more potent activity than the first-generation antiandrogens (ie, bicalutamide, flutamide, and nilutamide [Nilandron]).
PREVAIL Trial
Between September 2010 and September 2012, the PREVAIL trial randomly assigned 1,717 patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer who had not received previous chemotherapy to enzalutamide or placebo plus standard hormone therapy. Primary therapy for prostate cancer included surgery, radiation, and hormone therapy with a luteinizing hormone-releasing hormone agonist or first-generation antiandrogen.
The two primary endpoints were overall survival and radiographic progression-free survival. Enzalutamide reduced the risk of death by 29% (hazard ratio [HR] = 0.706, P < .0001), and reduced the risk of radiographic progression by 81% (HR = 0.186, P < .0001).
Overall response rate according to imaging of soft-tissue disease was 59% with enzalutamide (20% complete responses and 39% partial responses) vs 5% in the placebo group (P < .0001).
Enzalutamide treatment delayed the need for chemotherapy by a median of 17 months: Median time to chemotherapy was 28 months in the enzalutamide group vs 10.8 months in the placebo arm (HR = 0.35, P < .0001).
At an interim analysis in October 2013, the data were so convincing that that an Independent Data Monitoring Committee recommended that all patients on placebo be offered enzalutamide.
Adverse Events
Enzalutamide was well tolerated after 17 months of treatment, with the most common side effects being fatigue, constipation, and back and joint pain (mostly grade 1), as well as common side effects of hormone therapy (ie, weight gain and hot flashes). Grade 3 or higher adverse events were reported in 43% of the enzalutamide group vs 37% of the placebo group. Six percent of patients in both arms discontinued treatment due to adverse events.
When asked how these results stack up next to studies of abiraterone, Dr. Beer said, “I can’t make any blanket statements without head-to-head randomized trials. We now have two active drugs [in this setting]. My hope is that studies will help us further define the patient populations that benefit from these new drugs. For now, we have encouraging results [for both drugs], and clinicians will make decisions one patient at a time.”
He expects that studies will be planned to look at sequencing and combinations of these newer agents and also to study them earlier in the course of disease.
The study was sponsored by Medivation and Astellas. For full disclosures of the study authors, view the study abstract at www.gucasym.org.
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