BARCELONA—Investigators say they have confirmed the long-term efficacy and tolerability of an annual histrelin acetate implant in men with advanced prostate cancer.
The new results showed that histrelin subdermal implant, which was replaced every 12 months, maintained testosterone suppression initially documented at one year for a full four years without evidence of a surge in serum testosterone.
Neal Shore, MD, FACS, Director, Carolina Urologic Research Center/Atlantic Urology Clinics, Myrtle Beach, S.C., announced the findings at the 25th Anniversary European Association of Urology Congress.
Histrelin acetate is a synthetic luteinizing hormone-releasing hormone (LHRH) agonist that is available as an implant and is inserted subcutaneously under local anesthesia during an office-based procedure. After 12 months, the implant is removed and another may then be re-inserted if indicated.
Dr. Shore presented data from an extension trial that included 138 patients assigned to the histrelin arm in the original 52-week, phase 3 registration study. As a condition for continuation in the extension arm, all of the men had to have achieved the primary endpoint of testosterone suppression at four weeks.
“The take-home message is that the histrelin implant provides effective testosterone suppression over 12 months,” Dr. Shore pointed out. “Also, when replaced after 12 months, testosterone suppression is successfully maintained over the next 12 months.”
Histrelin only needs to be replaced after 12 months, so the implant has an edge over other LHRH agonists, which are usually administered by an injection into the muscle or under the skin and need to be repeated at one-, three-, four-, or six-month intervals, he added. “The need for repeated injections with multiple visits to the physician’s clinic may increase the risk of noncompliance and may also impact patient quality of life, specifically, patient and family time commitment, cost of travel, and reminder of their disease state,” he said. “Prospective validated questionnaires and trials are needed to further better understand the potential benefits of a longer acting depot formulation.”
Additionally, unlike other available LHRH agonists, the histrelin implant is nonbiodegradable. “An implant, as opposed to an injection, can be removed, if the treating physician chooses to cease androgen suppressive therapy,” he said.
At the time of enrollment in the original study, men were at least 45 years old with histologically confirmed stage III or IV prostate cancer, serum testosterone level of 150 ng/dl or greater, and a life expectancy of at least one year.
Men who did not have stage III or IV disease or men in whom staging could not be determined were eligible for inclusion if they had failed initial definitive therapy as evidenced by progressively increasing PSA.
Results showed that 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 suppressed below chemical castration levels (less than 50 ng/dL) throughout the extension period in all patients regardless of the duration of extension.
The implant was safe and well tolerated. As expected, the most common side effects were mild to moderate hot flashes.
“Overall, our extension data show that the once-year histrelin implant demonstrates effective and consistent suppression of serum testosterone with castrate levels achieved in all patients treated, without evidence of a significant surge in serum testosterone,” Dr. Shore commented.
The treatment, he said, is suitable for all prostate cancer patients who require 12 months or longer of testosterone suppression.