Experimental drug works faster than leuprolide in lowering testosterone in men with advanced PCa.
MILAN—The investigational agent degarelix provides more rapid and profound testosterone suppression than conventional androgen deprivation therapy in men with advanced prostate cancer, researchers reported. Degarelix is a new synthetic peptide gonadotropin-releasing hormone (GnRH) blocker.
The new findings are from a phase III trial comparing two doses of degarelix: 80 or 160 mg/month after an initial dose of 240 mg injected subcutaneously, to the GnRH agonist leuprolide depot, 7.5 mg/month injected intra-muscularly, over 12 months in 620 men with histologically confirmed prostate adenocarcinoma in whom androgen ablation was indicated.
“Androgen deprivation is the primary treatment for advanced prostate cancer and GnRH agonists are the most commonly used class of drugs,” said principal investigator Laurent Boccon-Gibod, MD, professor of urology at CHU Hôpital Bichat-Claude Bernard in Paris. “However, GnRH agonists are limited by their delayed effect on testosterone and PSA and an initial hormone surge with possible symptoms of flare.”
He reported findings here at the European Association of Urology 23rd Congress.
For inclusion, patients were re-quired to have serum testosterone levels greater than 1.5 ng/mL, an Eastern Cooperative Oncology Group (ECOG) score of 2 or less, and PSA level of 2 ng/mL or greater. The investigators defined a treatment response as suppression of testosterone to 0.5 ng/mL or less at monthly measurements from day 28 to day 364.
Both doses of degarelix were at least as effective as leuprolide at achieving a treatment response, and it had a quicker onset of action. By day 3, 97% of men receiving the 160-mg dose and 90% of men receiving the 80-mg dose had testosterone levels of 0.5 ng/mL or less compared with none of the leuprolide-treated patients. By day 14, all degarelix-treated patients achieved suppression of testosterone levels to 0.5 ng/mL or less compared with 18.2% in the leuprolide arm.
The experimental drug did not cause a testosterone surge or microsurge, and PSA levels decreased more rapidly with degarelix than with leuprolide. After 14 days of treatment, PSA levels had decreased in the degarelix arms by a median of 64% versus 18% in the leuprolide arm, researchers said.
Degarelix was well tolerated, and there were no serious adverse events considered to be related to the study treatment and no systemic allergic reactions. Injection site adverse events were more common in the degarelix groups.
“What we need are treatments that better mimic surgical castration, and degarelix seems to be as effective as orchidectomy,” John Anderson, MD, consultant urologic at the Royal Hallamshire Hospital in Sheffield, U.K., commented during a news conference. “Most men obviously prefer taking a drug than having their testicles removed, and this new drug can provide the same benefits as surgery but without the drawbacks.”
If degarelix were available, he added, the only conceivable reason a patient might continue to choose surgery over a drug treatment would be cost, but any cost differential would be overshadowed by the advantages of degarelix treatment. “Onetime surgery may be cheaper than chronic drug treatment, but the difference between the two options cost-wise is not that great,” he said. “A man wants quality of life, and he doesn’t want to lose his testicles because of health-care economy.”