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Patients with low- or intermediate-risk localized prostate cancer who received enzalutamide (Xtandi) monotherapy saw a reduced risk of cancer progression, according to a randomized phase II trial.

Among 227 patients on active surveillance (AS), treatment with enzalutamide reduced the risk of pathological or therapeutic prostate cancer progression by 46% compared with AS alone (HR 0.54, 95% CI 0.33-0.89, P=0.02), reported Neal Shore, MD, of Carolina Urologic Research Center in Myrtle Beach, South Carolina.

Enzalutamide monotherapy also delayed prostate-specific antigen (PSA) progression by 6 months versus AS alone (HR 0.71, 95% CI 0.53-0.97, P=0.03), they noted in .

This study "represents the first trial to compare the effects of a novel androgen receptor antagonist as monotherapy versus AS in patients with low-risk or intermediate-risk localized prostate cancer," Shore and team wrote. "Results suggest that enzalutamide may offer an alternative short-term treatment option for this patient population, potentially reducing the need for more aggressive treatment approaches."

In other findings, the odds of a negative biopsy were significantly higher at 1 year for enzalutamide patients (OR 3.5, 95% CI 1.76-6.92, P<0.001), and while there were more patients with a negative biopsy at 2 years, the difference was not statistically significant (OR 1.6, 95% 0.66-4.00, P=0.29).

Likewise, the odds of a secondary rise in serum PSA levels were significantly reduced at 1 year (OR 0.1, 95% CI 0.08-0.26, P<0.001), but not 2 years (OR 1.1, 95% CI 0.37-3.53, P=0.81).

In an , Susan Halabi, PhD, of Duke University Medical Center in Durham, North Carolina, and colleagues pointed out that outcomes between the two groups were similar at 2 years after cessation of enzalutamide, "suggesting that the natural history of the tumor may not have been altered but patients in the enzalutamide arm had different growth kinetics while receiving active enzalutamide treatment."

"Whether this will translate into substantially delaying or abrogating the need for definitive therapy for a cohort of patients will require longer follow-up," they added.

Patient-reported outcomes were not significantly worse with enzalutamide, with the exception of sexual and physical function, which resolved at 24 months after treatment cessation.

While the data are "encouraging," this study does not identify which patients will benefit from early intervention with enzalutamide, the commentators noted. "It is critical that patients with low-risk or intermediate-risk prostate cancer be followed for at least a decade with studies that are sufficiently powered to detect those differences in outcomes in various subsets of patients."

For this open-label study, 227 patients on AS from 66 U.S. and Canadian sites were randomized 1:1 to enzalutamide 160 mg or continued AS alone. From June 2016 to August 2020, patients were monitored for 1 year of treatment and up to 2 years of follow-up. Mean age was 66, 90% were white, and 9.3% were Black.

The primary endpoint was time to pathological or therapeutic prostate cancer progression. Secondary endpoints included incidence of a negative biopsy, incidence of a secondary rise in serum PSA levels at 1 and 2 years, and time to PSA progression.

Just 74.6% of the men treated with enzalutamide and 70.8% of those in the AS-alone arm completed 1 year of AS, "highlighting one of the challenges of AS protocols," Halabi and colleagues noted.

As for safety, patients treated with enzalutamide had a higher incidence of adverse events (AEs) than patients on AS alone (92.0% vs 54.9%) during the 1-year treatment period, most grade 1 or 2.

The most commonly reported AEs during treatment with enzalutamide were fatigue (55.4%), gynecomastia (36.6%), nipple pain (30.4%), breast tenderness (25.9%), and erectile dysfunction (17.9%), while the only AE that occurred in 5% or more of patients in the AS arm was hypertension (7.1%).

Drug-related AEs were reported in 99 men (88.4%), with 2.7% considered serious and 7.1% leading to study drug discontinuation.

Three patients in the enzalutamide arm died, none of whom were receiving the drug at the time of death, and none considered treatment-related.

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