For this trial, the primary endpoint was PSA nadir < 4 ng/ml after 7 months of therapy, as this has been recognized as a powerful surrogate for 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 included toxicity, biochemical and radiologic progression free survival (PFS), and OS.
Stratification was by presence of bone pain and race (AA vs other). PSA was monitored monthly for first 7 months and then every 3 months thereafter. The target sample size was 82 evaluable patients but the study was stopped early abiraterone when showed OS benefit in mHSPC [3,4]. Metastatic site biopsies were mandatory pretherapy and optional post therapy.
There were 71 men enrolled in the trial, 29 black, 41 white and one Asian. The median age was 67 years (range 46-87) and median baseline PSA was 56.3 ng/ml in Arm A (range 4.2-10,431 ng/ml) and 60 ng/ml (range 4.9-12,030 ng/ml) in Arm B. There were 27 pts (38.5%) that had bone pain and 13 with visceral metastases; no seizures were noted in either arm. Grade ≥3 AE’s for patients in Arm A were: Hypertension (13%), infection (7%), and syncope (7%) and for Arm B were: Hypertension (21%), fatigue (7%), and hematuria (7%). By intention to treat analysis 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 for Arms A and B were 86% and 79%, respectively. Among enrolled patients, 53 (75%) biopsy samples had tumor tissue available. TMPRSS-ERG fusion gene expression, CXCR4, and AKR1C3 levels were assessed in metastatic biopsies, showing differential patterns pre- and post-treatment and are possible biomarkers that may be further evaluated for correlation with clinical endpoints.
The authors concluded that early enzalutamide use in mHSPC has the potential to improve PSA remission rates. It remains to be elucidated whether these encouraging PSA response rates correlate to improved PFS and OS outcomes.
Presented by: Ulka Vaishampayan, Karmanos Cancer Center, Detroit, MI
Co-Authors: Lance K. Heilbrun, Paul Monk, Sheela Tejwani, Guru Sonpavde, Daryn Smith, Pallavi Jasti, Kimberlee Dobson, Elisabeth I. Heath, Michael L. Cher, Sreenivasa Chinni, Joseph A. Fontana
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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