Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer
- Study type
- Clinical trial
- Study name
- PROSPER
- Phase
- Phase 3
- Design
- Randomised, double-blind, phase 3 trial with 2:1 randomisation (enzalutamide versus placebo)
- Sample size
- 1401 patients
- Source
- N Engl J Med · 2018
- Trial registration
- NCT02003924
In plain words
This study was done in men whose prostate cancer had progressed despite hormone treatment and whose PSA was rising quickly, but in whom no spread (metastasis) could yet be seen on scans. Adding the drug enzalutamide to hormone treatment lengthened the time without metastasis from about 14.7 months to 36.6 months. Serious side effects were slightly more common in the enzalutamide group (31% vs 23%). The decision about this treatment should be made with your treating doctor.
Key results
Treatment arms and regimens
Enzalutamide 160 mg orally once daily with continued ADT, until radiographic progression or unacceptable toxicity (933 patients).
Placebo once daily with continued ADT (468 patients).
Source of the regimen details: Full text of the paper (PMC8288034) and ClinicalTrials.gov NCT02003924
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
1401 asymptomatic men with non-metastatic castration-resistant prostate cancer (on conventional imaging), continuing ADT with testosterone 50 ng/dL or less, PSA ≥2 ng/mL and PSA doubling time 10 months or less (median 3.7 months), ECOG performance status 0 or 1. A history of seizure or a condition predisposing to seizure, and significant cardiovascular disease, were exclusion criteria.
Endpoints
Primary endpoint: metastasis-free survival (time from randomisation to radiographic progression or to death without radiographic progression). Secondary endpoints reported in the abstract: time to first use of subsequent antineoplastic therapy, time to PSA progression and overall survival (first interim analysis).
Safety and side effects
Grade 3 or higher adverse events 31% versus 23%. Adverse events of special interest that were more frequent with enzalutamide: hypertension (12% versus 5%), major adverse cardiovascular events (5% versus 3%), cognitive disorders (5% versus 2%), and falls and non-pathological fractures (17% versus 8%). Discontinuation due to adverse events 10% versus 6%.
Clinical significance and place in guidelines
This trial showed that enzalutamide markedly reduces the risk of metastasis or death in non-metastatic castration-resistant prostate cancer with a short PSA doubling time (10 months or less). The abstract reports only the first interim overall survival analysis; the status of approvals and guideline recommendations should be checked separately.
Limitations
In the abstract, overall survival data were still immature, and only the first interim analysis is reported. Grade 3 or higher adverse events were more frequent in the enzalutamide group. The study population was limited to patients with a PSA doubling time of 10 months or less.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.