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Enzalutamide reduces risk for metastasis among men with castration-resistant prostate cancer
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Enzalutamide reduced risk for metastasis or death by 71% among men with nonmetastatic castration-resistant prostate cancer and rising PSA levels, according to results of a double-blind phase 3 trial.
Adverse events appeared consistent with those previously observed during treatment with enzalutamide (Xtandi; Astellas, Pfizer), a nonsteroidal antiandrogen medication approved for treatment of men with metastatic prostate cancer.
“I’m delighted with these results,” Maha Hussain, MD, FACP, FASCO, deputy director of Robert H. Lurie Comprehensive Cancer Center at Northwestern University and a HemOnc Today Editorial Board Member, said in a press release. “Not only did the drug reduce cancer spread, but many other disease-related effects were impacted.”
The trial included 1,401 men with nonmetastatic castration-resistant prostate cancer. Median time to PSA doubling among the cohort was 3.7 months.
Researchers randomly assigned men to receive 160-mg enzalutamide or placebo once daily.
Metastasis-free survival — defined as time from randomization to radiographic progression, or time to death without radiographic progression — served as the primary endpoint.
Median follow-up was 18.5 months for the enzalutamide group and 15.1 months for the placebo group. At data cutoff, 219 men (23%) assigned enzalutamide and 228 men (49%) assigned placebo had developed metastasis or died.
Researchers reported significantly longer median metastasis-free survival among men assigned enzalutamide than placebo (36.6 months vs. 14.7 months; HR = 0.29; 95% CI, 0.24-0.35).
Men assigned enzalutamide also achieved longer time to first use of antineoplastic therapy (39.6 months vs. 17.7 months; HR = 0.21; 95% CI, 0.17-0.26) and longer time to PSA progression (37.2 months vs. 3.9 months; HR = 0.07; 95% CI, 0.05-0.08).
By the first OS analysis, 103 patients (11%) assigned enzalutamide and 62 patients (13%) assigned placebo had died.
In the enzalutamide group, 219 men experienced a primary endpoint event; of those, 187 (85%) experienced radiographic progression and 32 (15%) died without radiographic progression.
In the placebo group, 228 men experienced a primary endpoint event; of those, 224 (98%) experienced radiographic progression and four (2%) died without radiographic progression.
“Our goal was to see if we could delay the reappearance of cancer with the hope that it will lead to prolonged life,” Hussain said in the press release. “We have to do more follow-up over time to see if long-term survival is impact, but there are early positive trends.”
A higher percentage of men assigned enzalutamide than placebo experienced grade 3 or higher adverse events (31% vs. 23%).
“Whereas radiographic progression-free survival has been standardized as an endpoint in metastatic settings, there was previously no earlier endpoint for nonmetastatic castration-resistant prostate cancer,” Julia A. Beaver, MD, assistant professor of oncology at Johns Hopkins Sidney Kimmel Cancer Center, and colleagues wrote in an accompanying editorial.
“The FDA has now recognized that a prolonged delay in development of metastatic disease is an objective and clinically relevant measure,” Beaver and colleagues added. “Future agents may be approved on the basis of metastasis-free survival only if substantial effects on this transition are demonstrated and the safety profile is acceptable for a medication taken long term.” –by Andy Polhamus
Disclosures: Hussain reports honoraria and travel fees from Sanofi; honoraria from OncLive and Physicians’ Education Resource; and grant support from AstraZeneca, Bayer, Genentech and Pfizer. Please see the study for all other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.
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