Enzalutamide Increases Time to First Skeletal-Related Event and Improves Quality-of-Life Outcomes in Castration-Resistant Prostate Cancer
In the phase III international AFFIRM trial, enzalutamide (Xtandi) was shown to improve overall survival vs placebo in men with metastatic castration-resistant prostate cancer after progression on docetaxel. In an analysis of secondary endpoints reported in The Lancet Oncology, Fizazi et al found that enzalutamide treatment was also associated with significantly prolonged time to first skeletal-related event and significant improvements in pain and health-related quality-of-life outcomes.
Study Details
In AFFIRM, 1,199 patients were randomly assigned 2:1 in double-blind fashion to receive enzalutamide at 160 mg/d (n = 800) or placebo (n = 399). Skeletal-related event was defined as radiation therapy or surgery to bone, pain was assessed using the Brief Pain Inventory-Short Form (BPI-SF) and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, and health-related quality of life was assessed using FACT-P.
Time to First Skeletal-Related Event
Skeletal-related events occurred in 36% of enzalutamide patients and 40% of placebo patients. Median time to first skeletal-related event was 16.7 vs 13.3 months (hazard ratio [HR] = 0.69, P = .0001). Skeletal-related event event-free rates at 1 year were 62.0% vs 52.9%.
Pain
Pain progression (increase in pain score) at week 13 occurred in 174 (28%) of 625 evaluable enzalutamide patients vs 101 (39%) of 259 placebo patients (difference= −11.2%, P = .0018). Median time to pain progression was not reached vs 13.8 months (HR = 0.56, P = .0004).
Enzalutamide patients had significantly better outcomes for pain severity (mean change in score from baseline = −0.15 vs +0.50, P < .0001) and pain interference (mean change in score from baseline = −0.01 vs +0.74, P < .0001). Pain palliation (≥ 30% reduction in pain score without an accompanying ≥ 30% increase in narcotic analgesic use) at week 13 was observed in 22 (45%) of 49 evaluable enzalutamide patients vs 1 (7%) of 15 placebo patients (P = .0079).
Health-Related Quality of Life
Overall improvement in health-related quality of life (≥ 10-point increase in global FACT-P score) occurred in 275 (42%) of 652 evaluable enzalutamide patients vs 36 (15%) of 248 placebo patients (P < .0001), with significantly greater proportions of enzalutamide patients having improvement on the physical well-being (31% vs 17%, P < .001), social or family well-being (32% vs 23%, P = .0084), emotional well-being (41% vs 21%, P < .001), functional well-being (42% vs 20%, P < .001), and prostate cancer subscales (55% vs 25%, P < .001). Enzalutamide patients also had a longer median time to health-related quality-of-life deterioration (≥ 10-point decrease in global FACT-P score or death from any cause; 9.0 vs 3.7 months, HR = 0.45, P < .0001).
The investigators concluded, “Our results show that, in addition to improving overall survival, enzalutamide improves wellbeing and everyday functioning of patients with metastatic castration-resistant prostate cancer.”
Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris Sud, Villejuif, is the corresponding author for The Lancet Oncology article.
The study was funded by Astellas Pharma and Medivation. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
