Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy
- Study type
- Clinical trial
- Study name
- AFFIRM
- Phase
- Phase 3
- Design
- Randomised, double-blind, placebo-controlled trial
- Sample size
- 1199 patients
- Source
- N Engl J Med · 2012
- Trial registration
- NCT00974311
In plain words
In this study, men with advanced prostate cancer whose disease was still not controlled by hormone treatments after chemotherapy received either enzalutamide tablets or a placebo. Those who took enzalutamide lived on average about 4.8 months longer (18.4 months versus 13.6 months). Tiredness, diarrhoea and hot flushes were more common in this group, and seizures were reported in a small number of patients (0.6%).
Key results
Treatment arms and regimens
Enzalutamide 160 mg orally once daily (4 × 40 mg capsules), until disease progression or unacceptable toxicity; continued castration (GnRH analogue or bilateral orchiectomy) (800 patients).
Matching placebo, orally once daily (399 patients).
Source of the regimen details: ClinicalTrials.gov NCT00974311 and the FDA label for XTANDI (DailyMed)
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
1199 men with metastatic castration-resistant prostate cancer who had previously received docetaxel chemotherapy; 2:1 randomisation stratified by ECOG performance status and pain intensity.
Endpoints
Primary endpoint: overall survival. Secondary endpoints: proportion of patients with a 50% or greater decline in PSA (prostate-specific antigen), soft-tissue response rate, quality-of-life response rate, time to PSA progression, radiographic progression-free survival and time to the first skeletal-related event.
Safety and side effects
According to the FDA label: grade 3 or higher adverse events in 47% of patients in the enzalutamide group; discontinuation due to adverse events 16%; the most common reason for discontinuation was seizure (0.9%). In the paper, seizures were reported in 5 patients (0.6%). Fatigue, diarrhoea and hot flushes were more frequent with enzalutamide.
Clinical significance and place in guidelines
This study showed that enzalutamide significantly prolongs survival in metastatic castration-resistant prostate cancer after chemotherapy, and it was also superior to placebo on all secondary endpoints. The status of drug approvals and current clinical guideline recommendations should be checked separately, as they are not mentioned in the abstract.
Limitations
The study was stopped after the planned interim analysis, and the upper limit of the confidence interval for median survival in the enzalutamide group had not yet been reached. The study population was limited to patients after chemotherapy. Other limitations are not stated in the abstract.
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.