Enzalutamide Monotherapy Induces PSA Response in Men with Hormone-Naïve Prostate Cancer

Share this content:

(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.

“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).


Clinicaltrials.gov Listing

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs