CUA 2018: PROSPER: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Enzalutamide in Men with nmCRPC

Halifax, Nova Scotia (UroToday.com) Fred Saad, MD, presented an overview of the PROSPER trial.1  Non-metastatic castration-resistant prostate cancer (nmCRPC) is an area of unmet need with no currently approved therapies. The risk of metastasis is associated with increasing baseline PSA and short PSA doubling time. Delaying time to all metastasis is clinically relevant, with a potential to delay cancer-related morbidity and prolong overall survival (OS). Enzalutamide significantly improved OS and radiographic progression-free survival (RPFS) in men with CRPC. Enzalutamide was superior to bicalutamide in improving RPFS in the subgroup of patients with chemotherapy -naïve nmCRPC (the STRIVE trial).2

The PROSPER study design is shown in Figure 1. Its primary endpoint was metastasis-free survival (MFS) in NMCRPC patients. Secondary endpoints included safety, time to PSA progression, time to use of new antineoplastic treatment, OS, PSA response, and quality of life. 

Figure 1 – PROSPER trial design:
UroToday CUA 2018 PROSPER 1
Baseline patient characteristics are shown in table 1. 

Radiographic progression was seen in 20% of the Enzalutamide arm compared to 48% of the placebo arm. The proportion of progression events in the Enzalutamide arm was 50% less than that of the placebo arm. Median MFS was ~22 months longer with Enzalutamide than with placebo (Figure 2). Also, time to PSA progression was ~33 months longer with Enzalutamide than with placebo (93% relative risk reduction) (Figure 3). Median time to first use of new antineoplastic therapy was ~22 months longer with Enzalutamide than with placebo (79% relative risk reduction) (Figure 4). The median follow-up for each arm was ~ 22 months and there was a 20% reduction in the relative risk of death with Enzalutamide vs. placebo, but this was not statistically significant. Adverse events as the primary reason for treatment discontinuation occurred in 9% of patients in the Enzalutamide arm compared to 6% of the placebo arm. No statistically or clinically meaningful changes in health-related quality of life were observed over 97 weeks.

Table 1 – Patient baseline characteristics:
UroToday CUA 2018 PROSPER 2
Figure 2 – Metastasis-free survival (MFS):
UroToday CUA 2018 PROSPER 3
Figure 3 – Time to PSA progression:
UroToday CUA 2018 PROSPER 4
Figure 4 – Time to first use of new antineoplastic therapy:
UroToday CUA 2018 PROSPER 5
Saad concluded his talk stating that in men with nmCRPC and rapid PSA doubling time (median of 3.7 months), Enzalutamide resulted in clinically meaningful and statistically significant 71% reduction in the relative risk of developing metastatic CRPC. Therapy was well tolerated, and adverse events were generally consistent with those reported in prior clinical trials in men with CRPC. All secondary endpoints except OS were significantly better with the Enzalutamide arm.  Median OS was not reached in either group in the first interim analysis. However, there was a 20% lower relative risk of death in the Enzalutamide group than in the placebo group.

References:
1. M Hussain, et al. J Clin Oncol 36, 2018 (suppl 6s; abstr 3)
2. DF Penson, et al. J Clin Oncol, 34; 2098-2106, 2016

Presented by: Fred Saad, MD, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia
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