The addition of enzalutamide, an oral androgen receptor inhibitor, to active surveillance for patients with low-risk or intermediate-risk localized prostate cancer reduced the risk of pathological or therapeutic prostate cancer progression when compared to active surveillance alone, in a phase 2 trial.

The open-label, phase 2 ENACT trial enrolled 114 patients with low-risk or intermediate-risk prostate cancer already undergoing active surveillance between June 2016 and August 2020 across 66 sites in the United States and Canada. The patients were randomized on a 1:1 basis to receive either 160 mg enzalutamide plus active surveillance (n = 114), or active surveillance alone (n = 113) for 1 year.

The primary end point of the study was time to pathological or therapeutic prostate cancer progression. Secondary end points included incidence of a negative biopsy result, percentage of cancer-positive cores, incidence of secondary rise in serum prostate-specific antigen (PSA) levels at 1 and 2 years, as well as time to PSA progression, and safety.

The median follow-up duration was 492.5 days for the enzalutamide arm and 270.5 days for the active surveillance alone arm. Enzalutamide reduced the risk of prostate cancer progression by 46% compared to active surveillance alone (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.33 to 0.89; P = .02).

The odds of a negative biopsy result were 3.5 times higher for those patients receiving enzalutamide compared to active surveillance alone. With enzalutamide, there was also a reduced percentage of cancer-positive cores, and reduced odds of a secondary rise in serum PSA levels at 1 year in treatment with enzalutamide with no significant difference observed at 2 years. PSA progression was significantly delayed by 6 months with enzalutamide compared to active surveillance (HR, 0.71; 95% CI, 0.53 to 0.97; P = .03).

The most common adverse events during enzalutamide treatment were fatigue in 55% of patients and gynecomastia in 36.6%. While there were 3 deaths in the enzalutamide arm, none of these patients were receiving the study drug at the time of death; no deaths were considered treatment-related.

Because enzalutamide was well tolerated and showed significant treatment response among this patient population, the study authors concluded that “enzalutamide may offer an alternative short-term treatment option for this patients population, potentially reducing the need for more aggressive treatment approaches.”

Source:

Shore ND, Renzulli J, Fleshner NE, et al. Active surveillance plus enzalutamide monotherapy vs active surveillance alone in patient with low-risk or intermediate-risk localized prostate cancer: The ENACT randomized clinical trial. JAMA Oncol. Published online June 16, 2022. doi:10.10011/jamaoncol.2022.1641