Histrelin Subdermal Implant Shows Sustained Efficacy in Prostate Cancer

by Jill Stein | Medscape.com | 04.26.2010

The gonadotropin-releasing hormone (GnRH) agonist histrelin acetate (VantasR), administered as a 50 mg subdermal implant once yearly, retained its effectiveness over four years of follow-up in men with advanced prostate cancer, according to data released here at the European Association of Urology 25th Annual Congress.

Results in patients enrolled in an extension trial following completion of a 52-week phase 3 trial showed that a histrelin subdermal implant, which was replaced every 12 months, maintained the testosterone suppression originally shown at one year for a full four years with no testosterone breakthrough.

"Successful and sustained testosterone suppression was obtained over four years with the use of a histrelin implant that was replaced every 12 months," Neal Shore, M.D., FACS, medical director of Carolina Urologic Research Center/Atlantic Urology Clinics in Myrtle Beach, South Carolina, told Medscape Urology.

"Histrelin implants also provide a benefit in terms of convenience because they only need to be replaced once yearly, whereas other GnRh agonists are given by injections that need to be repeated every one, three or six months."

The nonbiodegradable 3 cm × 3.5 mm histrelin implant is inserted under the skin of the inner aspect of the upper arm during a simple procedure. It is done under local anesthesia and takes approximately four minutes.

Dr. Shore and colleagues presented findings in 138 men who were enrolled in the histrelin group in the original phase 3 registration study, and who had achieved the primary end point of testosterone suppression at four weeks.

At the time of enrollment in the original study, patients had a median age of 74 years, histologically confirmed stage III or IV adenocarcinoma of the prostate, a serum testosterone level of 150 ng/dL or greater, and a life expectancy of at least one year.

The primary efficacy variable was the suppression of serum total testosterone concentration to levels below 50 ng/L.

Histrelin Implant Confers Consistent Testosterone Suppression

Patients who entered the extension phase received a total of 305 implants: 94 during the extension phase and 211 patients during the main study.

An average of three implants was inserted in each patient over the course of the extension trial.

Serum testosterone remained below chemical castration levels (less than 50 ng/dL) throughout the extension period in all patients, irrespective of the length of extension.

The most commonly reported adverse events were mild to moderate hot flashes, which are consistent with the "well-described" effects of testosterone suppression.

"Any patient requiring 12 months or longer of testosterone suppression is an ideal candidate for this treatment," Dr. Shore said in an interview.

"Level 1 evidence for the appropriateness of testosterone suppression within the urological literature correlates with clinical utilization in more than 80% of indicated prostate cancer patients," he added.

Quality of Life a Priority

"The study is important because it shows that a once-yearly treatment can safely provide ongoing efficacy in prostate cancer patients," Francois Desgrandchamps, M.D., director of the urology service at Hôpital Saint-Louis in Paris, France, told Medscape Urology.

He also noted that surveys show that prostate cancer patients regard quality of life as a top priority and prefer to maintain their normal routines without constant reminders of their disease.

"Each time a patient has a doctor's appointment, he is reminded of his disease," he said. "For patients on GnRH therapy, a once-yearly subcutaneous implant is obviously more appealing than an injection that needs to be repeated every month or every three or six months, because it means that patients are reminded less often of their disease."

Prostate cancer is the second most common cancer in men after lung cancer, and more than 670,000 new cases of prostate cancer are diagnosed annually worldwide. It is the second most common cause of cancer death in men in the United States, with roughly 29,000 deaths each year.

(The study was funded by Orion Pharma. Dr. Shore reports being an investigator/consultant for Orion Pharma. Prof. Desgrandchamps has disclosed no relevant financial relationships.)

European Association of Urology (EAU) 25th Annual Congress: Abstract 141. Presented on April 17, 2010.

Copyright Medscape.com 2010