October 23, 2023
Enzalutamide Monotherapy & Combination Preserves Quality of Life in Prostate Cancer
By Catlin Nalley
Recent findings showed that enzalutamide with or without leuprolide improved metastasis-free survival (MFS) while still preserving health-related quality of life among nonmetastatic hormone-sensitive prostate cancer (nmHSPC) patients with high-risk biochemical recurrence. This data from the Phase III EMBARK trial (NCT02319837) was presented by Stephen Freedland, MD, Director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, during the European Society for Medical Oncology (ESMO) Congress 2023, held October 20-24 in Madrid, Spain (Abstract 1766MO).
“In terms of how patients feel, we found no difference between these experimental therapies and the standard of care in terms of overall quality of life,” noted Freedland, who is also Professor of Urology at Cedars-Sinai, in a statement. “So we’re able to preserve patients’ quality of life, including one option that better preserved sexual function than the current standard of care, even on these extra-aggressive therapies that help patients live longer without disease progressing.”
Study Methods
EMBARK, which is a global, Phase III, randomized clinical trial, included patients with high-risk biochemical recurrence and non-metastatic hormone-sensitive prostate cancer after failed local therapy (n=1,068). High-risk was defined as a PSA doubling time of less than 9 months, according to Freedland. Other patient population characteristics included PSA ≥2 ng/mL above nadir post-radiotherapy and ≥1 ng/mL post-radical prostatectomy. Eligible patients were randomized 1:1:1 to enzalutamide plus leuprolide acetate (n=355), enzalutamide alone (n=355), and placebo plus leuprolide acetate (n=358).
Freedland and colleagues assessed patient-reported outcomes at baseline and every 12 weeks until the development of metastasis or death. The main objectives of this analysis were to assess treatment effects in time to first deterioration (TTFD) and time to first confirmed clinically meaningful deterioration (TTFCD). Researchers measured this via the Brief Pain Inventory Short Form (BPI-SF) worst pain and Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score using predefined thresholds.
Other objectives included the following: treatment effects in time to first deterioration and time to first clinically meaningful deterioration measured by the European Organization for Research and Treatment of Cancer QoL Questionnaire-Prostate 25 (QLQ-PR25) and European QoL 5-Dimensions 5-Levels (EQ-5D-5L) visual analogue scale (VAS).
In the intent-to-treat population, study authors made comparisons for enzalutamide + leuprolide acetate versus placebo + leuprolide acetate and enzalutamide alone versus placebo plus leuprolide acetate.
Key Results
Data from the EMBARK trial, which was recently published in the New England Journal of Medicine, demonstrated that patients who received enzalutamide alone or in combination with leuprolide acetate had improved metastasis-free survival when compared with those who received placebo plus leuprolide acetate (2023; doi: 10.1056/NEJMoa2303974). The quality of life analysis examining patient-reported outcomes offers a patient perspective on the disease/treatment experience not captured by clinical assessment, according to Freedland and colleagues, who set out to answer the question, “Are we sacrificing quality of life to get those oncological benefits?”
At baseline, 327-332 patients per group completed the PRO questionnaires. Completion rates over the study period were 85-95 percent. Freedland noted that all groups had high baseline health-related quality of life.
“No significant differences in time to first deterioration or time to first clinically meaningful deterioration were observed among treatment groups versus placebo plus leuprolide acetate in FACT-P total score or BPI-SF worst pain,” Freedland noted.
When looking at the FACT-P subdomains, the study authors found that the time to first clinically meaningful deterioration in the physical well-being subdomain score was significantly shorter for enzalutamide with or without leuprolide compared with placebo plus leuprolide. Additionally, the median time to first clinically meaningful deterioration in the prostate cancer subscale score and advanced prostate symptom index was significantly shorter for patients in the enzalutamide monotherapy cohort versus those in the placebo plus leuprolide arm. Freedland noted there was “no significant difference observed in time to first deterioration or time to first clinically meaningful deterioration for other FACT-P subdomains.”
While discussing QLQ-PR25 and EQ-5D-5L VAS, the study authors reported that the median TTCD in sexual activity score was significantly longer with enzalutamide monotherapy than with placebo plus leuprolide acetate. Freedland and colleagues observed a significantly shorter TTCD in the hormonal treatment-related symptoms score among patients treated with enzalutamide plus leuprolide acetate versus placebo plus leuprolide acetate. Data showed no significant differences in TTCD in the EQ-5D-5L VAS score in any treatment arm.
“In summary, enzalutamide combination and monotherapy both improved MFS without sacrificing quality of life,” Freedland stated. “There were no differences in our primary measure. We do see slightly more hormonal treatment symptoms with enzalutamide combination and sexual activity was slightly better preserved with enzalutamide monotherapy.”
This analysis of patient-reported outcomes in the EMBARK study was published simultaneously in NEJM Evidence (2023; doi:10.1056/EVIDoa2300251).
Catlin Nalley is a contributing writer.