For this trial, men with progressive mCRPC by Prostate Cancer Working Group 2 criteria were eligible. Prior treatment with taxanes for mCRPC (this study predated CHAARTED and STAMPEDE) and any prior treatment with enzalutamide or abiraterone plus prednisone was exclusionary. Patients were randomized 1:1 to enzalutamide or enzalutamide/abiraterone at standard FDA-approved doses. Randomization was stratified by prior chemotherapy and Halabi prognostic risk groups. The primary endpoint was overall survival (OS). Secondary endpoints included radiographic progression-free survival (rPFS) and on-treatment PSA declines. The primary analysis was based on the stratified log-rank test adjusting on the stratification factors. The trial design is as follows:
There were 1,311 men randomized between January 2014 and August 2016, including 657 to enzalutamide and 654 to enzalutamide/abiraterone. Groups were well balanced between arms, including stratification variables. Halabi risk groups included 15.6% of patients that were high-risk, 35.3% intermediate, and 48.1% low. At the time of analysis, 45.8% of patients were alive and 34.4% of patients had no progression. The median OS for enzalutamide was 32.5 months (95% CI 30.4-35.4) and 34.2 months (95%CI 31.8-37.5) for enzalutamide/abiraterone (p = 0.53). The hazard ratio for death was 0.90 (95%CI 0.78-1.05):
The median on-treatment radiographic progression-free survival (rPFS) was 25.2 months (95%CI 22.6-27.3) for enzalutamide/abiraterone compared to 20.7 months (95%CI 19.3-22.5) for enzalutamide alone, demonstrating a significant improvement favoring enzalutamide/abiraterone (HR 0.85, 95%CI 0.74-0.97).
However, there was also no difference in fifty percent PSA decline rates (80% vs. 76.5%):
Grade 3-5 adverse events (all attributions) were 55.6% for enzalutamide and 68.8% for enzalutamide/abiraterone. Treatment discontinuation due to adverse events occurred in 5% and 12%, patient withdrawal in 5% and 13%, for patients receiving enzalutamide and enzalutamide/abiraterone, respectively.
Dr. Morris concluded with several take-home messages:
- Adding abiraterone to enzalutamide does not improve OS relative to enzalutamide alone
- Enzalutamide/abiraterone has a modest improvement in rPFS
- On-treatment rPFS and OS were similar to previous studies
- Enzalutamide/abiraterone caused more adverse events than enzalutamide alone
- The current standard of care is unchanged by this study
Presented by: Michael J. Morris MD, Medical Oncologist, Clinical Director, Genitourinary Medical Oncology Service & Prostate Cancer Section Head, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Co-Authors: Glenn Heller, Alan Haruo Bryce, Andrew J. Armstrong, Himisha Beltran, Olwen Mary Hahn, Eric C. McGary, Paul Tracy Mehan, Amir Goldkorn, Bruce J. Roth, Han Xiao, Colleen Watt, David W. Hillman, Mary-Ellen Taplin, Charles J. Ryan, Susan Halabi, Eric Jay Small; Memorial Sloan Kettering Cancer Center, New York, NY; Mayo Clinic Arizona, Phoenix, AZ; Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; University of Chicago Medical Center, Chicago, IL; Kaiser Permanente, Cadillac, CA; Missouri Baptist Hosp, St Louis, MO; Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; Washington University School of Medicine, St. Louis, MO; Memorial Sloan Kettering Cancer Center, Basking Ridge, NJ; University of Chicago, Chicago, IL; Mayo Clinic Alliance Statistics and Data Center, Rochester, MN; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA; University of Minnesota, Minneapolis, MN; Duke University Medical Center, Durham, NC; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, @zklaassen_md, Georgia Cancer Center, Augusta University/Medical College of Georgia at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA