Long-term data from the PREVAIL trial (NCT01212991) confirm that enzalutamide improves survival compared with placebo in patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).
Enzalutamide reduced death risk by 17% (P <.001), despite 65%, 54%, and 43% of placebo-treated patients receiving subsequent docetaxel, abiraterone, and enzalutamide, respectively. Median overall survival at 5 years was 36 vs 31 months, respectively, Andrew J. Armstrong, MD, MSc, of Duke Cancer Institute at Duke University in Durham, North Carolina, and colleagues reported in European Urology.
Their prognostic model also showed a 5-year overall survival benefit from enzalutamide across risk groups: 42%, 24%, and 5% for the low-, intermediate-, and high-risk groups, respectively. Patients achieving lower PSA nadirs within 3 months with enzalutamide had better 5-year survival. Notably, relatively few men in the trial had visceral metastases at screening.
With respect to adverse events, enzalutamide was associated with higher overall fatality (6.9% vs 3.8%) and fatal cardiovascular events (1.6% vs 0.4%). Falls, fractures, and cardiovascular events occurred more among enzalutamide-treated patients.
Dr Armstrong’s team discussed the potential value of exercise in supporting heart health, maintaining a healthy body weight, reducing the risk of sarcopenia and metabolic syndrome, reducing hot flashes, improving bone health, and preventing fractures. The investigators also suggested denosumab or zoledronic acid for fracture prevention.
According to an accompanying editorial by Carmel Pezaro, BHB, MBChB, of Weston Park Hospital in Sheffield, United Kingdom, and colleagues, the latest data from the PREVAIL study confirm several core concepts in the treatment of advanced prostate cancer. One of these concepts is that PSA kinetics are important.. “Patients lacking a PSA or clinical response within the first 3 months of enzalutamide treatment should be monitored closely for progression or considered for alternative treatments.”
The new data also underscore that harbingers of a poor prognosis include a short time from diagnosis to progression despite androgen deprivation therapy, liver metastases, poor performance status, and significant cancer-related symptoms, the editorialists wrote..Further, active management of bone and cardiovascular health is an essential part of PCa treatment, and chemotherapy will likely be needed at some point.
“As we work towards the shared goal of helping our patients live longer and better,” Dr Pezaro and coauthors wrote, “we can use these mature data from PREVAIL to help communicate expected prognosis as well as short- and long-term potential toxicities with enzalutamide.”
Disclosure: This clinical trial was supported by Pfizer Inc. and Astellas Pharma, Inc., the co-developers of enzalutamide. Please see the original references for a full list of authors’ disclosures.
Armstrong AJ, Lin P, Tombal B, et al. Five-year survival prediction and safety outcomes with enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer from the PREVAIL trial. Eur Urol. 78:347-357. Published online June 15, 2020. doi:10.1016/j.eururo.2020.04.061
Mukherji D, Omlin A, Pezaro C. Living longer and better with advanced prostate cancer. Eur Urol. 78:358-359. Published online June 15, 2020. doi:10.1016/j.eururo.2020.05.020