The median metastasis-free survival time for patients with non-metastatic castration-resistant prostate cancer and rising prostate-specific antigen (PSA) levels treated with enzalutamide was nearly double that of the median metastasis-free survival time for patients in the same group treated with placebo (36.6. months vs 14.7 months, respectively, P = .001), according to research published in the New England Journal of Medicine.1
Though researchers determined treatment with enzalutamide cut the risk of metastasis or death by 71%, median overall survival was not reached in either the enzalutamide or placebo group. And while risk of death was 20% lower in the enzalutamide group versus the placebo group, the result was not statistically significant.
Patients were randomly assigned in a 2:1 ratio to receive either a 160 mg dose of enzalutamide or placebo once daily. Of the 1401 patients in the trial, 219 of 933 participants (23%) in the enzalutamide arm experienced metastasis or died, compared with 228 of 468 patients (49%) in the placebo group. The study completion date was June 28, 2017, approximately 4 years after the study was initiated.
Patients in the enzalutamide group demonstrated a longer time until the first use of a follow-up treatment with antineoplastic medications, and a smaller percentage of patients in the enzalultamide cohort required these medications to begin with, compared with patients in the placebo group (15% vs 48%). Time to PSA progression was greatly reduced for those who were given enzalutamide (37.2 months vs 3.9 months, P = .001).
While these data are encouraging, adverse events of grade 3 or more were higher in the enzalutamide treatment arm compared with the placebo group (31% vs 23%, respectively, which led to a higher frequency of trial discontinuation in the enzalutamide cohort. Two patient deaths in the enzalutamide arm were attributed to treatment with the medication. Other notable adverse effects that were observed in this cohort included hypertension, mental impairment, cardiovascular events, and falls, among others.
Three patients in the enzalutamide arm also had serious, drug-related convulsions, and 5 patients receiving enzalutamide were identified as having “noninfectious encephalopathy or delirium.”
Despite the appearance of these side effects, the authors concluded that there was “no decrease in quality of life associated with enzalutamide treatment.”
- Hussain M, Fizazi K, Saad F et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465-2474. doi: 10.1056/NEJMoa1800536