CHICAGO — Intermittent androgen deprivation was shown to be less effective than continuous androgen deprivation for patients with hormone-sensitive metastatic prostate cancer, according to results of a Phase 3 trial presented in a plenary session at the 2012 ASCO Annual Meeting.
Prior studies have established that castration resistance occurs in the majority of patients with hormone-sensitive metastatic prostate cancer treated with androgen deprivation, with a median survival of 2.5 to 3 years. Based on biologic and experimental data, replacing androgens before castration resistance has been suggested as a way to maintain prostate cancer androgen dependence. In experimental models, intermittent androgen deprivation prolonged time to castration resistance and early clinical trials indicated potential for better quality of life.
“Medical or surgical castration – otherwise known as hormone therapy or androgen deprivation – is the standard therapy for patients with metastatic hormone-sensitive disease,” said Maha Hussain, MD, FACP, professor of medicine and urology at the University of Michigan Comprehensive Cancer Center, at a press conference. “Despite a high response rate, most patients will end up progressing on hormone therapy to become castration resistant.”
To determine the efficacy of this intermittent androgen-deprivation approach, Hussain and colleagues enrolled 3,040 patients with hormone-sensitive metastatic prostate cancer. These patients were treated with 7 months of of continuous hormonal therapy. Patients who achieved a PSA of 4 ng/ml or less at months 6 and 7 were randomly assigned to receive intermittent hormonal therapy (770 patients) or continuous hormonal therapy (765 patients). Due to periodically-administered treatments, patients in the intermittent therapy group received about half the amount of hormonal therapy as those in the continuous therapy group.
According to the study results, grade 3/4 related adverse events were observed in 30.3% of intermittent androgen deprivation patients and 32.6% of continuous androgen-deprivation patients.
No interaction with therapy was significant (P>0.25) except suggestion with disease extent (P=0.08): extensive disease HR=0.96 (95% CI 0.79, 1.15, P=0.64); and minimal disease: HR=1.23 (95% CI 1.02, 1.48, P=0.035). Prostate cancer was the cause of death in 56% of continuous androgen deprivation and 64% intermittent androgen deprivation patients. OS by race did not differ (P=0.44).
“In this international randomized phase 3 trial, in patients with metastatic hormone-sensitive prostate cancer, survival with intermittent hormone therapy was inferior to survival with continuous hormone therapy,” said Hussain. “Specifically, we did not rule out a relative increase in the risk of death of 20% or greater for intermittent [patients] as compared [with patients with] continuous therapy with a 95% confidence. Because of these findings, continuous therapy continues to be the standard of care.”
Hussain added “in secondary analysis, intermittent therapy was found not to be inferior to continuous therapy in patients who had extensive disease; yet intermittent hormone therapy was significantly inferior to continuous therapy in patients with minimal disease. These observations certainly suggest potential inherent biological differences and warrant further evaluations.”
For more information:
Hussain M. Abstract #4. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: The researchers reported funding from multiple pharmaceutical companies, including Abbott Laboratories, Astellas Pharma, Merck Serono, Millennium, NCCN and Pfizer.