As reported in JAMA Oncology by Neal D. Shore, MD, FACS, and colleagues, the phase II ENACT trial has shown a reduced risk of disease progression with the addition of enzalutamide to active surveillance in patients with low- or intermediate-risk localized prostate cancer.
Study Details
In the open-label trial, 217 patients receiving active surveillance from sites in the United States and Canada were randomly assigned between June 2016 and August 2020 to receive enzalutamide at 160 mg daily for 1 year with continued active surveillance (n = 114) or continued active surveillance alone (n = 113).
Neal D. Shore, MD, FACS
The primary endpoint was time to pathologic or therapeutic disease progression. Pathologic progression was defined as a ≥ 1 increase in primary or secondary Gleason pattern or ≥ 15% increase in cancer-positive cores; therapeutic progression was assessed as the earliest occurrence of primary therapy for prostate cancer.
Disease Progression
Median follow-up was 492.5 days (range = 1.0–1078.0 days) in the enzalutamide group and 270.5 days (range = 1.0–806.0 days) in the active surveillance group. Pathologic or therapeutic progression was observed in 28.1% of patients in the enzalutamide group vs 37.2% of the active surveillance group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.33–0.89, P = .02). Rates were 7.9% vs 23.0% (odds ratio [OR] = 0.3, 95% CI = 0.11–0.60, P < .01) during year 1 and 16.0% vs 16.4% during year 2 (OR = 0.9, 95% CI = 0.36–2.24, P = .81).
During year 1, the enzalutamide group had a higher rate of negative biopsy results (OR = 3.5, P < .001), a reduction in percentage of cancer-positive cores (P < .001), and lower likelihood of secondary increase in prostate-specific antigen (PSA) level (OR = 0.1, P < .001). During year 2, no significant differences in these measures were observed between groups. Median time to PSA progression was 14.82 months in the enzalutamide group vs 8.80 months in the active surveillance group (HR = 0.71, 95% CI = 0.53–0.97, P = .03).
Adverse Events
During the 1-year enzalutamide treatment period, the most common adverse events of any grade in the enzalutamide group were fatigue (55.4%), gynecomastia (36.6%), nipple pain (30.4%), breast tenderness (25.9%), and erectile dysfunction (17.9%); the only adverse event occurring in ≥ 5% of the active surveillance group was hypertension (7.1%). Grade ≥ 3 adverse events occurred in 9.8% vs 8.8% of patients. Death occurred in three patients in the enzalutamide group (due to homicide, intracranial hemorrhage, and metastatic cholangiocarcinoma) who were not receiving enzalutamide at time of death; no deaths were considered related to treatment.
KEY POINTS
- Enzalutamide plus active surveillance reduced the risk of disease progression vs active surveillance alone.
- Benefits in negative biopsy results, percentage of cancer-positive cores, and secondary increases in PSA were observed at 1 year.
The investigators concluded, “The results of this randomized clinical trial suggest that enzalutamide monotherapy was well tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer. Enzalutamide may provide an alternative treatment option for patients undergoing active surveillance.”
Dr. Shore, of Carolina Urologic Research Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Astellas Pharma Inc and Pfizer Inc. For full disclosures of the study authors, visit jamanetwork.com.
