Dr Freedland on Treatment Suspension and HRQoL During the EMBARK Trial in nmHSPC

Stephen J. Freedland, MD, director, the Center for Integrated Research in Cancer and Lifestyle, associate director, Training and Education, the Samuel Oschin Comprehensive Cancer Institute; the Warschaw, Robertson, Law Families Chair in Prostate cancer, professor, the Department of Urology, at Cedars-Sinai, discusses the correlation between treatment suspension and health-related quality of life (HRQoL) in patients with high-risk biochemically recurrent, nonmetastatic hormone-sensitive prostate cancer (nmHSPC) who were enrolled on the phase 3 EMBARK trial (NCT02319837), which investigated enzalutamide (Xtandi) with or without leuprolide vs leuprolide plus placebo.

Prior reports from the EMBARK trial demonstrated that enzalutamide, with or without leuprolide, significantly delayed metastasis-free survival compared with placebo plus leuprolide while maintaining high global HRQoL in this patient population. A post-hoc analysis was conducted to further examine the correlation between treatment suspension and HRQoL, focusing on pain and global quality of life, Freedland begins.

In this trial, treatment was suspended at week 37 for patients with a prostate-specific antigen (PSA) level below 0.2 ng/mL. Treatment was reinstated if PSA levels rose to 2.0 ng/mL or higher following radical prostatectomy or to 5.0 ng/mL or higher without radical prostatectomy. Using the intention-to-treat analysis, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks until disease progression. Longitudinal changes in HRQoL from treatment suspension at week 37 and from subsequent assessments conducted up to week 205 were also evaluated.

HRQoL data through week 109 were presented at the 2024 ASCO Annual Meeting, and confirmed that treatment suspension did not lead to clinically meaningful changes in the majority of PRO domains, indicating that these aspects were likely not heavily impacted by treatment initially, Freedland reports. Furthermore, hormonal treatment-related adverse effects (AEs) were shown to rapidly improve in all arms following treatment suspension; however, these AEs did worsen after week 97, Freedland notes. These findings suggest that, despite adverse effects, administration of enzalutamide with or without leuprolide can delay metastasis or improve survival without worsening HRQoL during or after treatment, Freedland explains.

For patients with nonmetastatic disease who do not exhibit symptoms from cancer or local progression, maintaining a high quality of life is crucial, Freedland emphasizes. It is therefore essential to discuss this balance between efficacy and quality of life with patients to ensure they receive therapies that prolong survival and delay disease progression without compromising their well-being, he concludes.