Top-line results from a large phase III trial support a potential role for enzalutamide (XTANDI) as treatment for non-metastatic castration-resistant prostate cancer.
Top-line results from the phase III PROSPER trial support a potential role for enzalutamide (XTANDI) as treatment for non-metastatic castration-resistant prostate cancer (CRPC).
The efficacy analysis showed that the study met its primary endpoint by demonstrating that the combination of enzalutamide plus androgen deprivation therapy (ADT) was associated with a statistically significant improvement in metastasis-free survival (radiographically detected metastasis). Thus, enzalutamide becomes the first androgen receptor inhibitor to show in a randomized, controlled trial improvement in metastasis-free survival in men with non-metastatic CRPC.
“When the full PROSPER results are available, they will hopefully confirm metastasis-free survival is significantly improved for men who received enzalutamide plus ADT compared to men receiving ADT alone. While there are currently no FDA-approved treatments for men who have non-metastatic CRPC, we may have an agent in the future that will allow us to treat these men earlier, rather than waiting for them to develop confirmed radiographic metastatic disease,” said PROSPER investigator and steering committee member Neal Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, SC.
“A delay in the development of metastatic cancer is important in the journey of a prostate cancer patient. To have the option to prescribe a once-a-day therapy that can be taken with or without food, and without stringent laboratory requirements, would provide flexibility for the provider and the patient.”
A preliminary analysis of adverse event data collected in PROSPER identified no new safety signals associated with enzalutamide. According to the findings, enzalutamide’s safety profile was consistent with that reported in previous clinical trials.
“When the final analysis is done, I do not anticipate seeing any difference in the safety profile of enzalutamide compared to what has been seen in earlier trials in which it was evaluated in men with metastatic CRPC,” Dr. Shore said.
“We didn’t see any new safety signals for enzalutamide in the phase II TERRAIN trial that enrolled asymptomatic or minimally symptomatic men with disease progression on ADT, and we found that the treatment arm of enzalutamide was superior to the comparator bicalutamide [Casodex] arm in terms of disease progression for this metastatic castrate-resistant prostate cancer population.”
PROSPER has a randomized, double-blind, placebo-controlled design and is being conducted at study sites in the United States, Canada, Europe, South America, and the Asia Pacific region. It enrolled approximately 1,400 patients who were randomized to treatment with enzalutamide, 160 mg once daily plus ADT, or ADT plus placebo.
Eligible patients were on ongoing ADT with a gonadotropin-releasing hormone agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration). They were to have PSA ≥2.0 ng/mL, PSA doubling time ≤10 months, Eastern Cooperative Oncology Group performance status of 0 or 1, and estimated life expectancy ≥12 months. Men who had received prior cytotoxic chemotherapy were excluded as were those who used hormonal therapy or biologic for prostate cancer (other than approved bone targeting agents and gonadotropin-releasing hormone agonist/antagonist therapy) or use of an investigational agent within 4 weeks of randomization.
An amendment to the PROSPER protocol in June 2017 revised the plan for the analyses of the primary and several secondary endpoints, which allowed for a reduction in the target sample size and accelerated completion of the clinical trial by 2 years.
Dr. Shore is a consultant and researcher for Amgen, Astellas, Bayer, Dendreon, Janssen, Pfizer, and Sanofi.
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