The addition of enzalutamide to androgen deprivation significantly reduced the risk for metastases or death among men with nonmetastatic castration-resistant prostate cancer, according to results of the phase 3 PROSPER trial presented at Genitourinary Cancers Symposium.
Enzalutamide (Xtandi; Astellas, Medivation), an androgen receptor inhibitor, is approved in the United States for treatment of men with metastatic castration-resistant prostate cancer.
The randomized, phase 3, double-blind, placebo-controlled PROSPER trial included 1,401 men with nonmetastatic castration-resistant prostate cancer that progressed as determined by rising PSA (PSA 2 at screening; median PSA doubling time 10 months) despite ADT. The men had no symptoms and no evidence of metastatic disease.
Researchers assigned men 2:1 to ADT plus 160-mg once-daily enzalutamide, or ADT plus placebo. Metastasis-free survival served as the primary objective.
Median treatment duration was 18.4 months among those assigned enzalutamide plus ADT vs. 11.1 months for those assigned placebo plus ADT.
Patients assigned enzalutamide plus ADT achieved significantly longer median metastasis-free survival (36.6 months vs. 14.7 months; HR = 0.29; 95% CI, 0.24-0.35).
“[For] patients with nonmetastatic castration-resistant prostate cancer, there is a high unmet need to delay development of metastases and the progression to advanced prostate cancer,” Maha Hussain, MD, professor of medicine at Robert H. Lurie Comprehensive Cancer Center at Northwestern University and a HemOnc Today Editorial Board Member, said in a press release issued by Pfizer and Astellas. “There are currently no approved systemic therapies for patients with nonmetastatic castration-resistant prostate cancer in the United States. ... If approved, [enzalutamide plus ADT] may provide men with nonmetastatic castration-resistant prostate cancer an important new treatment option.”
Secondary endpoints in the PROPSER trial included time to PSA progression, time to first use of new antineoplastic therapy and OS.
Patients assigned the combination demonstrated a 93% reduction in relative risk for PSA progression (HR = 0.07; 95% CI, 0.05-0.08), as well as longer median time to PSA progression (37.2 months vs. 3.9 months) and longer median time to first use of new antineoplastic therapy (39.6 months vs. 17.7 months; HR = .021; 95% CI, 0.17-0.26).
Median OS had not been reached in either treatment group. Results of a first interim analysis showed a trend in favor of the enzalutamide regimen, but the difference did not reach statistical significance (HR = 0.8; 95% CI, 0.58-1.09).
Adverse events in the PROSPER trial appeared consistent with those reported in prior clinical trials of enzalutamide for men with metastatic castration-resistant prostate cancer.
A higher percentage of enzalutamide-treated patients experienced any-grade adverse events (87% vs. 77%), grade 3 or higher adverse events (31% vs. 23%) and serious adverse events (24% vs. 18%). The most common grade 3 or higher adverse events were hypertension (5% for enzalutamide plus ADT vs. 2% for ADT alone) and fatigue (3% vs. 1%).
Five percent of enzalutamide-treated patients and 3% of patients assigned ADT alone experienced major adverse cardiovascular events. Three patients assigned enzalutamide experienced seizures compared with none of those assigned ADT alone.
Nine percent of patients assigned enzalutamide plus ADT and 6% of those assigned ADT alone discontinued treatment due to adverse events.