CHICAGO, IL USA (UroToday.com) - Presented by Matthew R. Smith, MD, PhD at the American Society of Clinical Oncology (ASCO) Annual Meeting - May 31 - June 4, 2013 - McCormick Place - Chicago, IL USA
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Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC)
Matthew Raymond Smith, Michael Borre, Per Rathenborg, Patrick Werbrouck, Hendrik Van Poppel, Axel Heidenreich, Peter Iversen, Edwina Baskin-Bey, Frank Perabo, De Phung, Bertrand Tombal
Departments of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Boston, MA; Department of Urology, Århus University Hospital, Skejby, Denmark; Department of Urology, Herlev Hospital, Herlev, Denmark; Department of Urology, AZ Groeninge Kortrijk, Kortrijk, Belgium; Department of Urology, University Hospitals Leuven, Leuven, Belgium; Department of Urology, RWTH University, Aachen, Germany; Department of Urologuy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Astellas Pharma Global Development, Inc., Staines, United Kingdom; Astellas Pharma Global Development, Inc., Leiderdorp, Netherlands; Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Background: In locally-advanced prostate cancer, the antiandrogen bicalutamide (Bic) is used to maintain quality of life relative to castration therapy (LHRHa), but efficacy as a monotherapy is limited. ENZA is an oral androgen receptor (AR) inhibitor with higher AR–binding affinity vs Bic, and it prevents nuclear translocation, shows no DNA binding, and induces apoptosis. ENZA was approved in the US after prolonging overall survival in post-docetaxel metastatic castration resistant prostate cancer. This phase 2 study assessed ENZA monotherapy in patients (pts) with HNPC and noncastrate testosterone (T) ≥ 230 ng/dL.
Methods: Pts with any stage HNPC (ECOG PS 0, life expectancy .1 y) requiring hormonal therapy received ENZA 160 mg/d for 25 wks. Primary endpoint was PSA response (≥ 80% decline at wk 25). Other endpoints were endocrine levels, pharmacokinetics, safety, and metabolic changes (body composition, bone biomarkers, lipids, and glycemic profiles).
Results: 67 pts were enrolled. Median age was 73 y; 39% had metastases, 36% and 24% had prior prostatectomy and radiation, respectively. ENZA levels reached steady state after ~4 wks. Mean changes in metabolic outcomes at wk 25 included: –0.24% total body bone mineral density (BMD), –4.15% lean body mass, 6.85% fat body mass, 14.75% bone alkaline phosphatase, 4.55% total cholesterol, 6.48% triglycerides, –1.98% A1c, –0.10% fasting glucose, and 45.06% HOMA-IR. At wk 25, PSA response was 93% (62/67; 95% CI, 86%–99%); median PSA decrease was –99.6%. Mean T and estrogen increased 114% and 72%, respectively; other endocrine increases were observed, the highest was 185% for luteinizing hormone. Most common treatment-emergent AEs were grade 1 and included gynecomastia (36%), fatigue (34%), nipple pain (19%), and hot flush (18%). Five pts had serious AEs (none drug related).
Conclusions: ENZA monotherapy achieved a high PSA response rate and marked PSA decline with efficacy similar to castration. In contrast to castration, BMD remained stable and metabolic variables (fat body mass, lipid and glycemic profiles) were not substantially impacted with ENZA monotherapy over the 6 month study period. Endocrine changes and AEs were consistent with potent AR inhibition. Clinical trial information: NCT01302041.
Dr. Matthew R. Smith is associate professor of medicine at Harvard Medical School and the director of genitourinary medical oncology at Massachusetts General Hospital Cancer Center in Boston.
He earned his medical degree at Duke University, and completed his training in internal medicine at Brigham and Women's Hospital and in medical oncology at Dana-Farber Cancer Institute.
Dr. Smith is the recipient of numerous awards, including a Midcareer Investigator Award from the National Institutes of Health and competitive research awards from the Prostate Cancer Foundation and Lance Armstrong Foundation. He has been published in a number of journals, including Journal of Clinical Oncology, Cancer, Urology, Journal of Urology and the New England Journal of Medicine.