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Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC).
J Clin Oncol 31, 2013 (suppl; abstr 5001)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
Abstracts by M. R. Smith:
Association of alkaline phosphatase (ALP) with clinical outcomes in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results from COU-AA-302.
Denosumab for the prevention of symptomatic skeletal events in patients with castration-resistant advanced prostate cancer: A comparison with skeletal-related events.
Enzalutamide monotherapy: Extended follow-up of a phase II study in hormone-naive prostate cancer patients.
Educational Book Articles by M. R. Smith:
Presentations by M. R. Smith:
Effect of denosumab on prolonging bone-metastasis-free survival (BMFS) in men with nonmetastatic castrate-resistant prostate cancer (CRPC) presenting with aggressive PSA kinetics.Session: General Poster Session B: Prostate Cancer (General Poster Session)
Effect of denosumab on prolonging bone-metastasis-free survival (BMFS) in men with nonmetastatic castrate-resistant prostate cancer (CRPC) presenting with aggressive PSA kinetics.Session: Oral Abstract Session A: Prostate Cancer (Oral Abstract Session)
Meeting: 2010 Genitourinary Cancers Symposium
Session: General Session II: Prostate Cancer - Integrated Care for High-risk Disease (General Session)