TY - JOUR
T1 - Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial
AU - Armstrong, Andrew J.
AU - Lin, Ping
AU - Tombal, Bertrand
AU - Saad, Fred
AU - Higano, Celestia S.
AU - Joshua, Anthony M.
AU - Parli, Teresa
AU - Rosbrook, Brad
AU - van Os, Steve
AU - Beer, Tomasz M.
N1 - Publisher Copyright:
© 2020 European Association of Urology
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - Enzalutamide
KW - Metastatic castration-resistant prostate cancer
KW - Multivariable model
KW - Overall survival
KW - Prostate-specific antigen
KW - Safety
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UR - http://www.scopus.com/inward/citedby.url?scp=85086108031&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2020.04.061
DO - 10.1016/j.eururo.2020.04.061
M3 - Article
C2 - 32527692
AN - SCOPUS:85086108031
SN - 0302-2838
VL - 78
SP - 347
EP - 357
JO - European Urology
JF - European Urology
IS - 3
ER -