In PREVAIL, men with mCRPC were randomized to enzalutamide (n = 872) or placebo (n = 845). For the purposes of this study, men were grouped into categories of confirmed maximal PSA decline from baseline at month 3 of treatment: no decline/decline < 30%, ≥ 30% decline, ≥ 50% decline, or ≥ 90% decline. Confirmation required PSA decline on ≥ 1 consecutive visit after month 3. Best overall soft-tissue response (per RECIST v1.1) was determined for patients with measurable disease at baseline. Time to PSA progression, rPFS (per PCWG2) and OS were estimated using the Kaplan-Meier method. Nearly 2/3 of men in the placebo arm (66%, 558/845) had no PSA decline/decline < 30%, in contrast to 11% (94/872) in the enzalutamide arm. In the enzalutamide arm, 81% (701/872) of men had a PSA decline of ≥ 30% from baseline at week 13, 73% (639/872) had a PSA decline of ≥ 50% and 35% (307/872) had a PSA decline of ≥ 90%. For men in the enzalutamide arm experiencing ≥ 50% PSA decline, the best objective soft-tissue response (partial or complete response) was 74.8% (95%CI 59.2-79.9), median time to PSA progression was 13.9 months (95%CI 13.8-16.6), HR for rPFS vs no decline/<30% decline was 0.17 (95%CI 0.11-0.27), and HR for OS vs no decline/<30% decline was 0.28 (95%CI 0.20-0.39). PSA flare (rise followed by a fall) after 3 months was rare with enzalutamide (< 1%).
In conclusion, PSA declines after 3 months of enzalutamide therapy are strongly associated with soft-tissue response and improvements in rPFS and OS, particularly for PSA responses >50%. Providing updated prognostic information to chemotherapy-naïve men with mCRPC can be of clinical value given the heterogeneity of long-term outcomes.
- Loriot Y, Miller K, Sternberg CN, et al. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (PREVAIL): Results from a randomised, phase 3 trial. Lancet Oncol 2015;16(5):509-521.
- Beer TM, Armstrong AJ, Rathkopf D, et al. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: Extended Analysis of the Phase 3 PREVAIL Study. Eur Urol 2017;71(2):151-154.
Co-Authors: P. Lin (San Francisco, United States of America) C. S. Higano (Seattle, United States of America) P. Iversen (Copenhagen, Denmark) C. N. Sternberg (Roma, Italy) B. Tombal (Brussels, Belgium) D. Phung (Leiden, Netherlands) T. Parli (San Francisco, United States of America) A. Krivoshik (Northbrook, United States of America) T. M. Beer (Portland, United States of America)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain