An update on the PROSPER trial analyzing enzalutamide plus androgen deprivation therapy found a lower risk of death than placebo for patients with non-metastatic CRPC.
Enzalutamide treatment presented a clinically meaningful 27% lower risk of death than placebo for patients with non-metastatic CRPC, according to a presentation from the 21st Annual Meeting of the Society of Urologic Oncology (SUO).
The PROSPER trial also found consistent adverse events with the previously established safety profile of enzalutamide, and the overall survival (OS) rates were similar across all 3 trials (PROSPER, SPARTAN, and ARAMIS). Metastases-free survival (MFS) benefits were also associated with the improved OS rates.
“All of the results from these trials support that treating patients earlier is better, and we can seriously improve overall survival,” Cora N. Sternberg, MD, FACP, clinical director at the Englander Institute for Precision Medicine, said in her presentation. “These trials have been reflected in the treatment recommendations from the AUA, which gives strong recommendations, and NCCN, category 1 recommendations, to use these novel hormonal agents in the nonmetastatic CRPC setting.”
In regard to MFS, the data found that enzalutamide treatment resulted in a 71% lower risk of radiographic progression or death when compared to placebo (HR, 0.29; 95% CI, 0.24-0.35). More, there was a 22-month increase in MFS from 14.7 months with placebo to 36.6 months with enzalutamide. Median follow-up for the enzalutamide group was 18.5 months while the placebo group saw a median follow-up of 15.1 months.
There was a statistically significant association of enzalutamide and OS, with a 27% reduction in the risk of death for patients in the enzalutamide group compared to placebo. Median survival for the enzalutamide group was 67 months compared to 56.3 months for placebo (HR, 0.73; 95% CI, 0.61-0.89). Median follow-up was approximately 48 months.
The primary end point of the research was MFS, with secondary end points of OS, time to PSA progression, safety, PSA response and quality of life.
“This survival difference was present even though 84% of patients from the placebo group received at least 1 subsequent anti-neoplastic therapy after the study was unblinded,” explained Sternberg. “This includes the 87 patients who received enzalutamide during the open-label extension.”
The PROSPER trial enrolled 1401 men with nonmetastatic CRPC defined by bone and CT scans who were randomized to receive either enzalutamide plus androgen deprivation therapy (n = 933) or placebo plus androgen deprivation therapy (n = 468).
As for adverse events, median treatment duration was more than twice as long in the enzalutamide group (33.9 months) than in the placebo group (14.2 months). The incidence of adverse events within the first 3 and 6 months of treatment was higher in the enzalutamide group (65% and 76%, respectively) than in the placebo group (52% and 64%, respectively).
The researchers noted that starting treatment earlier for these patients could improve survival rates and that new standards of care are emerging in the non-metastatic CRPC space.
“We know that in studies with enzalutamide, abiraterone, and apalutamide, giving treatment earlier to these patients improves overall survival,” said Sternberg. “For patients who are asymptomatic, we believe that the time to delay and time to metastases, the time to symptoms and time to chemotherapy is also beneficial.”
Sternberg CN. Nonmetastatic CRPC: PROSPER Trial Updates. Presented at: 21st Annual Meeting of the Society of Urologic Oncology; December 3, 2020.