(ChemotherapyAdvisor) – Monotherapy with the oral androgen receptor inhibitor, enzalutamide, was associated with significant prostate-specific antigen (PSA) response in men with hormone-naïve prostate cancer, results of a phase 2 study presented during the 4th annual Genitourinary Cancers Symposium in Orlando, FL, have found.

Enzalutamide is approved in the United States for the treatment of men with docetaxel-resistant metastatic castration-resistant prostate cancer (CRPC), Bertrand Tombal, MD, PhD, Chairman of the Division of Urology and Professor of Urology and Physiology at the Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium, and colleagues reported. In this population, the agent has been shown to increase overall survival by 4.8 months compared with placebo (hazard ratio [HR], 0.63).

Preclinical studies have shown enzalutamide has a higher androgen receptor binding affinity than bicalutamide.

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“In contrast to previous phase 2 and 3 studies that exclusively enrolled patients with CRPC receiving androgen deprivation therapy (ie, testosterone levels ≤ 50 ng/dL), this phase 2 study assessed the efficacy and safety of enzalutamide monotherapy in patients who had never received hormone therapy; presenting with non-castrate testosterone levels (≥ 230 ng/dL),” Dr. Tombal stated.

The 25-week open-label, single-arm study enrolled 67 men with hormone-naive, histologically confirmed prostate cancer of all stages who required hormonal treatment. Also required was a baseline Eastern Cooperative Oncology Group performance status score of 0 and a life expectancy greater than 1 year.

Median age was 73 years (range, 48-86 years); 39% of patients had metastases. Prior to study entry, 36% had undergone prostatectomy and 24% were treated with radiotherapy. All patients received enzalutamide 160 mg/day without concomitant castration. Primary end point was PSA response (>80% decrease at week 25); secondary end points included changes in endocrine levels and safety/tolerability.

The PSA response rate was 93%, Dr. Tombal reported, with a median decrease of −99% (range, −100%, −57%) at week 25. Compared with baseline, serum testosterone levels increased by a median of 113% (range, −32%, 300%) and estrogen levels, 58% (range, −49%, 321%) at week 25.

Mostly grade 1 or 2 drug-related adverse events (AEs) were reported by 82% of the study participants. The most frequent treatment-emergent AEs were gynecomastia (36%), fatigue (34%), and hot flushes (18%). A total of 7% of the men experienced serious AEs; however, none were drug-related.

Endocrine level changes and most common AEs (gynecomastia, fatigue, and hot flushes) were consistent with potent AR inhibition, Dr. Tombal concluded.

The 2013 Genitourinary Cancers Symposium is co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).


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