Randomized trial of enzalutamide versus bicalutamide in combination with androgen deprivation in metastatic hormone sensitive prostate cancer: A Prostate Cancer Clinical Trials Consortium trial.
Vaishampayan UN, Heilbrun LK, Monk P, Tejwani S, Sonpavde G, Smith D, Jasti P, Dobson K, Heath EI, Cher ML, Chinni S, and Fontana JA. Randomized trial of enzalutamide versus bicalutamide in combination with androgen deprivation in metastatic hormone sensitive prostate cancer: A Prostate Cancer Clinical Trials Consortium trial. J Clin Oncol 2018; 36(6)
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Background: Addition of abiraterone or docetaxel has overall survival (OS) benefit in metastatic hormone sensitive prostate cancer (mHSPC). The clinical outcomes with early enzalutamide in mHSPC are unknown. We compared the combinations of enzalutamide (Arm A) or bicalutamide (Arm B) each with LHRH analogue therapy in mHSPC. Methods: The primary endpoint was PSA nadir < 4 ng/ml after 7 months of therapy, as this has been recognized as a powerful surrogate for overall survival (OS) outcomes. A minimum of 29 African American (AA) patients were required to be enrolled to evaluate the effect of race on the primary endpoint. Secondary endpoints were toxicities, biochemical and radiologic progression free survival (PFS), and OS. Stratification was by presence of bone pain and race; AA or other. PSA was monitored monthly for first 7 months and then every 3 months. The target sample size was 82 evaluable patients but the study was stopped when early abiraterone showed OS benefit in mHSPC. Metastatic site biopsies were mandatory pretherapy and optional post therapy. Results: 71 men; 29 black, 41 white and 1 Asian were enrolled. The median age was 67 years (range 46-87 years) and median baseline PSA was 56.3 ng/ml in Arm A (4.2-10,431 ng/ml) and 60 (4.9-12,030 ng/ml) in Arm B. 27 pts (38.5%) had bone pain and 13 had visceral metastases. No seizures were noted in either arm. Grade 3+ AE's on Arm A were: Hypertension (13%), infection (7%), and Snycope (7%) and on Arm B were: Hypertension (21%), Fatigue (7%), and Hematuria (7%). By intent to treat PSA nadir < 4ng/ml at month 7 was achieved in 96.3% pts in arm A and 66.7% pts in arm B and in 71.7% of AA men and 89.7% of Caucasians. The 6-month PSA remission duration rates after month 7 on Arms A and B were 86% and 79%, respectively. 53 (75%) biopsy samples had tumor tissue available. Tmprss2-Erg fusion gene expression and androgen biosynthetic enzyme levels were determined in metastatic biopsies and will be correlated with clinical endpoints. Conclusions: Early enzalutamide use in mHSPC has the potential to improve PSA remission rates and subsequently improve PFS and OS outcomes.