2018 GU CANCERS SYMPOSIUM: Antiandrogenic Therapy in Nonmetastatic Castration-Resistant Prostate Cancer
Results from the phase III PROSPER trial in patients with nonmetastatic castration-resistant prostate cancer were presented by Hussain et al at the 2018 Genitourinary Cancers Symposium (Abstract 3). The results show that the use of enzalutamide (Xtandi) plus androgen-deprivation therapy (ADT) significantly reduced the risk of developing metastases or death by 71% compared to ADT alone. The median for the primary endpoint, metastasis-free survival, was 36.6 months for men who received enzalutamide compared to 14.7 months with ADT alone (n = 1,401; hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.24–0.35; P < .0001).
“In 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. There are currently no approved systemic therapies for patients with nonmetastatic castration-resistant prostate cancer in the United States,” said Maha Hussain, MD, Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and first author of the study. “In the PROSPER trial, treatment with enzalutamide plus ADT delayed the development of metastases compared to standard-of-care ADT alone and, if approved, may provide men with nonmetastatic castration-resistant prostate cancer an important new treatment option.”
Other Trial Findings
PROSPER also investigated time to prostate-specific antigen (PSA) progression, time to first use of new antineoplastic therapy, and overall survival as key secondary endpoints. The analysis demonstrated that patients who received enzalutamide plus ADT had a 93% reduction in relative risk of PSA progression compared to patients who received ADT alone (HR = 0.07, 95% CI = 0.05–0.08; P < .0001). Enzalutamide plus ADT delayed the median time to PSA progression by 33.3 months: 37.2 months (95% CI = 33.1–not reached) vs 3.9 months (95% CI = 3.8–4.0) with ADT alone.
Enzalutamide plus ADT prolonged the median time to first use of new antineoplastic therapy by 21.9 months vs ADT alone: 39.6 months (95% CI = 37.7–not reached) vs 17.7 months (95% CI = 16.2–19.7), a 79% relative risk reduction (HR = 0.21, 95% CI = 0.17–0.26; P < .0001). At the time of the first interim analysis, median overall survival had not yet been reached in either treatment arm. However, these interim results demonstrated a trend in favor of enzalutamide that was not statistically significant (HR = 0.80, 95% CI = 0.58–1.09; P = .1519).
Safety and Adverse Events
Adverse events in the PROSPER trial were generally consistent with those reported in prior enzalutamide clinical trials in patients with metastatic castration-resistant prostate cancer. Grade 3 or greater adverse events were reported in 31% of men treated with enzalutamide plus ADT and in 23% of men treated with ADT alone.
The most common (≥ 2%) grade 3 or greater adverse events that were reported more often in enzalutamide-plus-ADT–treated patients included hypertension (5% vs 2%) and fatigue (3% vs 1%). Major adverse cardiovascular events were reported in 5% of patients who received enzalutamide plus ADT and 3% with ADT alone. Three seizures (< 1%) were reported in patients who received enzalutamide plus ADT, and none were reported for those who received ADT alone. Treatment discontinuation was low in both study arms (9% with enzalutamide plus ADT vs 6% with ADT alone).
More About PROSPER
The phase III randomized, double-blind, placebo-controlled, multinational trial enrolled approximately 1,400 patients with nonmetastatic castration-resistant prostate cancer at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region. PROSPER enrolled patients with prostate cancer that had progressed (based on a rising PSA level) despite ADT but who had no symptoms and no prior or present evidence of metastatic disease. The trial evaluated enzalutamide at a dose of 160 mg taken orally once daily plus ADT vs placebo plus ADT.
The primary endpoint of the PROSPER trial, metastasis-free survival, is a measure of the amount of time that passes until a cancer can be radiographically detected as having metastasized, or until death within 112 days of treatment discontinuation. Secondary endpoints included time to PSA progression, time to first use of antineoplastic therapy, and overall survival.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
