Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial

Andrew J. Armstrong, Ping Lin, Bertrand Tombal, Fred Saad, Celestia S. Higano, Anthony M. Joshua, Teresa Parli, Brad Rosbrook, Steve van Os, Tomasz M. Beer

    Research output: Contribution to journalArticlepeer-review

    6 Scopus citations

    Abstract

    Background: In the PREVAIL study, enzalutamide significantly improved clinical outcomes versus placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Objective: To evaluate long-term benefits and risks of enzalutamide in the final prespecified PREVAIL analysis. Design, setting, and participants: We conducted a final 5-yr survival analysis of PREVAIL in men with chemotherapy-naïve mCRPC from the enzalutamide (n = 689) and placebo (n = 693) arms. Outcome measurements and statistical analysis: Predictors of the primary outcome of overall survival were estimated using the Kaplan-Meier method. Long-term adverse events over time were analyzed. Results and limitations: At the 5-yr data cutoff, 1382 of 1717 (80%) men had died. Enzalutamide reduced the hazard of death by 17% (hazard ratio 0.83; 95% confidence interval [CI] 0.75–0.93; p < 0.001), despite 65%, 54%, and 43% of placebo-treated patients receiving subsequent docetaxel, abiraterone, and enzalutamide, respectively. Median overall survival was 36 mo (95% CI 34–38) in the enzalutamide arm versus 31 mo (95% CI 29–34) in the placebo arm, with a median follow-up of 69 mo. Prognostic modeling showed 5-yr survival rates of 42%, 24%, and 5% for low-, intermediate-, and high-risk groups, respectively. Greater degrees of confirmed prostate-specific antigen declines (≤3 mo) were associated with greater 5-yr survival. A higher incidence of fatal treatment-emergent adverse events was observed with enzalutamide (6.9% vs 3.8%), with an increase in fatal cardiovascular events (1.6% vs 0.4%). Conclusions: With >5 yr of follow-up, enzalutamide continued to demonstrate improved survival in patients with mCRPC despite crossover and multiple subsequent effective therapies, balanced against a slightly higher rate of fatal cardiovascular events. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. Patient summary: We report a maintained long-term survival benefit with enzalutamide and risks with >5 yr of enzalutamide treatment and follow-up in men with metastatic prostate cancer, and identify groups of men with widely different outcomes based on clinical factors.

    Original languageEnglish (US)
    Pages (from-to)347-357
    Number of pages11
    JournalEuropean Urology
    Volume78
    Issue number3
    DOIs
    StatePublished - Sep 2020

    Keywords

    • Enzalutamide
    • Metastatic castration-resistant prostate cancer
    • Multivariable model
    • Overall survival
    • Prostate-specific antigen
    • Safety

    ASJC Scopus subject areas

    • Urology

    Fingerprint Dive into the research topics of 'Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial'. Together they form a unique fingerprint.

    Cite this