medwireNews: The ENACT trial has demonstrated a significantly reduced risk for progression with the use of enzalutamide in men with low- or intermediate-risk localized prostate cancer undergoing active surveillance (AS).
The treatment was also well tolerated, say the investigators in JAMA Oncology, and they add: “The trial results suggest that enzalutamide monotherapy may offer a potential treatment option for this patient population.”
The authors of a related commentary note, however, that “[w]hile these data highlight a decreased risk in progression of prostate cancer in some patients undergoing AS, it raises many questions, particularly concerning the selection of those patients most likely to benefit from treatment with enzalutamide and appropriate end points to make that judgement.”
Susan Halabi (Duke University, Durham, North Carolina, USA) and co-authors continue: “We look forward to additional data on this important and timely topic.”
In this open-label, phase 2 study, 227 men (median age 65 years) receiving AS for low- (53.3%) or intermediate-risk (46.7%) disease were randomly assigned to receive enzalutamide 160 mg/day for a year or not receive it. The primary endpoint of the study was time to pathologic or therapeutic progression, where the former was defined as a 1 point or greater increase in the primary or secondary Gleason pattern or at least a 15% increase in cancer-positive cores, and the latter as any use of primary therapy for prostate cancer.
After a median follow-up of 492.5 days in the enzalutamide plus AS group and 270.5 days in the AS alone group, the median time to pathologic or therapeutic progression was unreached in both groups, but the risk for progression was reduced by a significant 46% with the use of the androgen receptor inhibitor.
The proportion of men who experienced pathologic or therapeutic progression at the 1-year mark was significantly lower in the enzalutamide plus AS arm than the AS alone arm, at 7.9% versus 23.0%, but the rates were comparable at 2 years, at 16.0% and 16.4%, respectively.
Neal Shore (Carolina Urologic Research Center, Myrtle Beach, South Carolina, USA) and co-researchers report that the addition of enzalutamide also significantly improved several secondary endpoints, such as the incidence of a negative biopsy result, the percentage of cancer-positive cores, and the incidence of a secondary rise in serum prostate-specific antigen levels.
But again, these improvements were significant at the 1-year but not the 2-year timepoint, they highlight.
For instance, 35.1% of patients who received enzalutamide plus AS had a negative biopsy finding at the 1-year mark compared with 14.2% of those who underwent AS alone, a significant difference. But the rates were a comparable 19.0% and 12.0% at 2 years.
“It is interesting that on the cessation of treatment with enzalutamide, the differences in the 2 arms at year 2 seemed to be very similar, 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,” say Halabi and fellow commentators.
“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 add.
Reporting on the safety, Shore et al say that the observed adverse event (AE) data were “consistent with the known safety profile” of enzalutamide.
During the 1-year treatment period, AEs of any grade occurred in a higher proportion of patients given enzalutamide plus AS than those who received AS alone, at 92.0% versus 54.9%, but the incidence of grade 3 or worse AEs was similar, at a respective 9.8% (10 grade 3, one grade 5) and 8.8% (nine grade 3, one grade 4).
The most common any-grade AE in the enzalutamide group was fatigue, observed in 55.4% of patients, followed by gynecomastia (36.6%), nipple pain (30.4%), breast tenderness (25.9%), and erectile dysfunction (17.9%).
Shore and colleagues highlight that none of the three deaths in the enzalutamide arm that occurred during the treatment and follow-up periods were considered related to the study drug or attributed to disease progression.
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