Dr Freedland on the Next Steps for Evaluating Enzalutamide in Prostate Cancer

"Several questions arise [based on the data from EMBARK]. [First], EMBARK was [conducted in] the pre–prostate-specific maturation antigen [PSMA] era. We’re now in the PSMA era, so what would we do if a patient showed 1 or 2 spots of metastases on a PSMA scan?"

Stephen Freedland, MD, a professor, a urologic surgeon, and the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai; as well as associate director of Education & Training and director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer Institute, discussed the phase 3 EMBARK trial (NCT02319837) evaluating the efficacy and safety of enzalutamide (Xtandi) with leuprolide in patients with high-risk, biochemically recurrent, nonmetastatic hormone-sensitive prostate cancer (nmHSPC) at high risk for metastasis.

The trial enrolled patients with no metastases on bone scans, CT scans, or MRIs per central imaging negative. Of note, prostate-specific antigen (PSA) responders, defined as those achieving a PSA expression level less than 0.2, were permitted to suspend treatment at week 37.

Data from EMBARK give rise to several next steps for evaluating enzalutamide as a potential new standard of care in biochemically recurrent prostate cancer, Freedland stated. Topics that require more exploration include reducing adverse effects (AEs) with enzalutamide in combination with leuprolide, increasing the efficacy of enzalutamide as monotherapy, investigating the viability of repeated treatment suspensions, and adding radiation to the regimen.

Freedland also emphasized the intensity of the drug combination as a priority. Although enzalutamide plus leuprolide is showing encouraging efficacy, reducing AEs associated with this intensified regimen should be a priority, Freedland asserted, adding that this could potentially be achieved through the use of repeated treatment suspensions.

Freedland added that the efficacy of the enzalutamide combination also makes withholding other treatments like radiation from patients even harder. More research is needed to confirm the feasibility of administering this combination alongside radiation while keep AEs at bay, he said.

Conversely, Freedland noted the need to improve the efficacy of enzalutamide. In EMBARK, enzalutamide plus leuprolide reduced the risk of death by 40.3% compared with leuprolide alone (HR, 0.597; 95% CI, 0.444-0.804; P = .0006); improvements in overall survival (OS) were not statistically significant with enzalutamide monotherapy (HR, 0.83; 95% CI, 0.63-1.095; P = .1867). Despite meeting several secondary end points and being well tolerated in patients with nmHSPC, figuring out how to significantly improve OS with enzalutamide alone is a key next step for future research.

Disclosures: Freedland reported having consultant roles with Astellas Pharma Inc., AstraZeneca, Bayer, Eli Lilly, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck, Novartis, Pfizer Inc., Sanofi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), and Tolmar.