The addition of abiraterone or docetaxel has shown overall survival (OS) benefit in mHSPC. There is adequate rationale for clinical efficacy of enzalutamide and ADT combination in mHSPC. We compared the combination of enzalutamide (Arm A) or bicalutamide (Arm B), each with ADT in mHSPC.
The primary endpoint was the seven month PSA remission (SMPR), with PSA nadir of < 4 ng/ml, as this is an accepted surrogate for overall survival (OS) outcomes. Secondary endpoints were toxicities, biochemical and radiologic progression free survival (PFS), and OS. Stratification was by presence of bone pain (yes/no) and race; (AA or other). PSA was monitored monthly for first 7 months and then every 3 months. Metastatic site biopsies were mandatory pretherapy and optional post therapy.
71 men; 29 African American (AA),41 Caucasian 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. 26 pts (39%) had bone pain and 37(52%) had extensive disease. Predominant grade 3+ adverse events on Arm A were: Hypertension (13%), infection (7%), and syncope (7%) and on Arm B were: Hypertension (21%), Fatigue (7%), and Hematuria (7%). No seizures were noted. PSA nadir < 4ng/ml at month 7 was achieved in 29/31 (94%) pts in arm A and 16/24 (67%) pts in arm B. 53% on arm A and 43% on Arm B continue to maintain PSA< 4 ng/ml. 4 (11%) deaths have occurred on enzalutamide arm as compared to 13 (37.1%) deaths on Arm B. Among AA patients, SMPR was 100% on Arm A and 46% on Arm B. 53 (75%) biopsy samples had tumor tissue available. TMPRSS-ERG fusion gene and CXCR4 expression and androgen biosynthetic enzyme levels were determined in metastatic biopsies. Patients with low copy number of ERG had an increased likelihood of SMPR (19/20 or 95%) as compared to high copy number (14/20 or 70%).
Early enzalutamide use in mHSPC improved PSA remission rates and has the potential to subsequently improve OS outcomes High ERG copy number was associated with decreased SMPR. This is the first randomized trial to report efficacy results of the combination of ADT and enzalutamide compared with ADT and bicalutamide in mHSPC.
Clinical trial identification
Legal entity responsible for the study
Karmanos Cancer Center.
U.N. Vaishampayan: Research support, consulting: Astellas Inc. P. Monk, G. Sonpavde, S. Chinni: Research support: Astellas Inc. All other authors have declared no conflicts of interest.