Enzalutamide Improves Survival in Men With Metastatic Prostate Cancer

By Will Boggs MD

July 06, 2020

NEW YORK (Reuters Health) - Enzalutamide improves five-year survival in men with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but increases the risk of fatal adverse events, according to final results from the PREVAIL trial.

"When docetaxel was FDA (Food and Drug Administration) approved as the first life-prolonging therapy for men with metastatic castration resistant disease back in 2004, the 5-year survival was less than 5% of these men," said Dr. Andrew J. Armstrong of Duke Cancer Institute, in Durham, North Carolina.

"The gratifying data from this PREVAIL trial of enzalutamide shows that many more men with mCRPC are living past 5 years, with 42% of lower-risk men and nearly a quarter of intermediate-risk men," he told Reuters Health by email.

PREVAIL was stopped after a preplanned interim analysis revealed enzalutamide superiority compared with placebo in terms of survival and radiographic progression-free survival. At that point, eligible placebo patients were invited to cross over to enzalutamide in an open-label extension.

In the current study, Dr. Armstrong and colleagues evaluated long-term safety and efficacy of enzalutamide and five-year survival estimates based on pretreatment prognostic factors and risk groups, as well as posttreatment declines in PSA.

Placebo patients who crossed over to enzalutamide in the extension study were included in the placebo group for the final analysis of overall survival.

At the five-year overall survival analysis, enzalutamide reduced the hazard of death by 17% compared with placebo (P<0.001). At a median follow-up of 69 months, median overall survival was 36 months in the enzalutamide group versus 31 months in the placebo group, the researchers report in European Urology.

Enzalutamide maintained a long-term survival advantage over placebo despite 68% of placebo-treated men receiving subsequent enzalutamide or abiraterone.

Only among men with baseline liver metastases did enzalutamide not appear to confer an overall survival advantage.

Based on an updated 11-factor prognostic model, five-year survival rates decreased with increasing risk group, from 42% for the low-risk group to 24% for the intermediate-risk group and 5% for the high-risk group.

Similarly, five-year survival rates increased with greater drops in prostate-specific antigen (PSA) after treatment (from 9% for men with no PSA decline to 67% for men whose PSA declined to undetectable levels).

Men treated with enzalutamide had higher rates of treatment-emergent adverse events leading to death (6.9% vs. 3.8% with placebo), fatal cardiovascular treatment-emergent adverse events (1.6% vs. 0.4%), and drug-related fatal cardiovascular events (two cases, or 0.2%, vs. none with placebo).

The prognostic model used to stratify patients in this study is available as an online calculator that can provide patient-specific information to guide communications and goals for care at https://www.mdcalc.com/prevail-model-prostate-cancer-survival.

"While no prognostic model is perfect, and treatment advances every year are pushing survival beyond current expectations, it is important to have the most up-to-date estimates of risk for patient communications," Dr. Armstrong said. "This calculator can also be invaluable for the design of new treatments which intend to beat these expectations, particularly in those men with higher risk metastatic prostate cancers."

"We still need better treatment for high-risk men in this setting, as these patients still have a less than 5% 5-year survival," he said.

Dr. Philip Kantoff of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical School, in New York City, who studies advanced prostate cancer, told Reuters Health by email, "Enzalutamide has life-prolonging effect in men with metastatic castration-resistant prostate cancer but has toxicity including increased rates of non-cancer death. Risks and benefits need to be balanced and individualized."

He added that enzalutamide is "one of multiple options for men, including abiraterone, apalutamide, and darolutamide."

Pfizer Inc. funded the study and had financial ties to all of the authors.

SOURCE: https://bit.ly/37CGvWJ European Urology, online June 9, 2020.