medwireNews: Men with localized prostate cancer and high-risk biochemical recurrence benefit from treatment with enzalutamide, either alongside leuprolide or alone, suggest phase 3 trial data.
The researchers report in The New England Journal of Medicine that outcomes such as metastasis-free survival (MFS), time to prostate-specific antigen (PSA) progression, and time to first use of antineoplastic therapy were significantly improved with the androgen receptor inhibitor.
Moreover, “[t]he safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life,” they add.
Writing in an accompanying editorial, Ana Aparicio (University of Texas MD Anderson Cancer Center, Houston, USA) says that despite challenges such as the heterogeneity of prostate cancer, “the results of the EMBARK trial do support that, in a subgroup of men with biochemical recurrence, the benefits of early cancer control with systemic therapy outweigh its risks.”
She continues: “In addition to developing more effective drugs with fewer toxic effects, tilting the scale to maximize benefit will require better predictors of prostate cancer lethality and treatment effect.”
The trial included 1068 men who had biochemical recurrence after primary therapy for localized prostate cancer and a PSA doubling time of 9 months or less. Participants were randomly assigned to receive enzalutamide 160 mg daily alongside leuprolide 22.5 mg every 12 weeks, leuprolide alone, or enzalutamide.
After a median follow-up of 60.7 months, the primary endpoint of MFS in the enzalutamide plus leuprolide group versus the leuprolide group alone significantly favored the combination, with 5-year rates of 87.3% and 71.4%, respectively. This equated to a significant 58% reduction in the risk for imaging-based progression or death with the addition of enzalutamide.
The 5-year MFS rate was also significantly higher with enzalutamide monotherapy than leuprolide alone, at 80.0% versus 71.4%, and a 37% reduction in the risk for imaging-based progression or death, report Neil Shore (Carolina Urologic Research Center, Myrtle Beach, South Carolina, USA) and fellow EMBARK investigators.
The proportion of patients who were free from PSA progression at 5 years was significantly higher in the enzalutamide combination and monotherapy arms than in the leuprolide alone arm, at 97.4% and 88.9% versus 70.0%, respectively.
This was also the case for the proportion free from use of antineoplastic therapy at 5 years, with corresponding rates of 83.0%, 75.7%, and 61.7%.
At the 5-year mark, the rate of overall survival was 92.2% in the enzalutamide combination group, 89.5% in the enzalutamide monotherapy group, and 87.2% in the leuprolide alone group. The hazard ratios for death for the comparison of the combination and monotherapy regimens with leuprolide alone numerically favored enzalutamide, at 0.59 and 0.78, respectively, but did not reach statistical significance.
Shore and colleagues note that “[n]o substantial difference was noted in the time to first deterioration of [Functional Assessment of Cancer Therapy–Prostate] total scores in the combination group or the monotherapy group as compared with the leuprolide-alone group.”
And they add that there were no new safety signals. The most common adverse event (AE) in the enzalutamide combination and leuprolide alone groups was hot flashes, occurring in 68.8% and 57.3% of participants, respectively, followed by fatigue in 42.8% and 32.8%. The most frequent AEs in the enzalutamide monotherapy group were fatigue and gynecomastia, in 46.6% and 44.9%, respectively.
Men in the enzalutamide monotherapy group were more likely to experience nipple pain and breast tenderness (15.3 and 14.4%, respectively) than those in the enzalutamide combination (3.1 and 1.4%) and leuprolide alone (1.1 and 1.1%) arms.
But most AEs “were mild-to-moderate in severity,” highlight the researchers.
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