Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC).

Genitourinary (Prostate) Cancer
Session Type and Session Title: 
Clinical Science Symposium, The Future of Androgen Pathway Targeting in Prostate Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 5001)
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

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Abstract Disclosures


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.