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Continuous androgen deprivation therapy confers a survival advantage over intermittent therapy in men with metastatic prostate cancer.
Chicago-Continuous androgen deprivation therapy confers a survival advantage over intermittent therapy in men with metastatic prostate cancer, according to recently announced results from a large multicenter international trial.
Although continuous ADT has been the standard of care in men with metastatic hormone-sensitive prostate cancer, intermittent therapy had gained favor in an effort to curb side effects, with the belief that efficacy would not be affected or may even be enhanced.
But the present study's findings "demonstrate that survival with intermittent hormonal therapy is not comparable to continuous therapy for patients with metastatic prostate cancer," said Dr. Hussain, professor of medicine and urology, associate director for clinical research, and co-leader of the prostate cancer/genitourinary oncology program at the University of Michigan Comprehensive Cancer Center, Ann Arbor, who said that the data are likely to change practice.
"This finding is striking and surprising because it goes against the conventional belief based on all of the trials that have been done thus far," she said at the American Society of Clinical Oncology annual meeting in Chicago.
This international study, sponsored by the National Cancer Institute, included 1,535 patients with newly diagnosed hormone-sensitive metastatic prostate cancer whose serum PSA level declined to 4.0 ng/mL or less after 7 months of continuous hormonal therapy with goserelin acetate (Zoladex) in combination with bicalutamide (Casodex). After stratifying the patients by disease extent, performance status, and prior hormone therapy, they were randomly assigned to receive intermittent or continuous ADT.
The median age of the patients was 70 years. About half had extensive disease and half had minimal disease.
The study was designed to confirm non-inferiority of intermittent ADT; however, non-inferiority was not confirmed, said Dr. Hussain.
After a median follow-up of 9.2 years, median overall survival was 5.1 years in the group assigned to intermittent therapy versus 5.8 years for those assigned to continuous therapy, for a hazard ratio (HR) of 1.09, which did not meet the criterion for non-inferiority because the upper limit of the 95% CI, 1.24, extends beyond the pre-specified non-inferiority threshold of 1.20 (specifically, a 20% or greater increased risk of death could not be ruled out with 95% confidence). Forty-two percent in the continuous therapy arm were still alive at 7 years compared with 38% of the arm randomized to intermittent therapy.
A secondary analysis incorporating several clinical and prognostic factors revealed that for men with minimal disease spread, the difference in survival between the two groups was even greater. In this subset, median overall survival was 5.2 years in those on intermittent therapy versus 7.1 years for those who received continuous therapy. The HR for death with intermittent therapy was 1.23, which again did not meet the criterion for non-inferiority.
Among men with more extensive disease spread, median survival was similar in the two arms (5 years with intermittent vs. 4.4 years with continuous therapy).
There were no differences in the rate of grade 4 treatment-emergent adverse events.
Better sexual function in intermittent arm
A quality of life substudy conducted in 615 of the patients found better overall sexual function in patients who received intermittent therapy compared with continuous therapy. Patients randomized to continuous ADT reported more impotence, lower libido, and worse emotional function than those assigned to intermittent androgen deprivation (p<.01 for all).
Previous clinical trials comparing continuous and intermittent ADT were underpowered to evaluate survival, said William K. Oh, MD, associate director for clinical research, Tisch Cancer Institute at the Mount Sinai School of Medicine, New York.
"Neither this nor any randomized trial has shown a superior cancer outcome with intermittent androgen deprivation therapy," said Dr. Oh, who was not involved with the study. Therefore, the preclinical concept that intermittent therapy is as good as continuous therapy "must no longer be propagated."
Dr. Hussain has received research funding from Abbott Laboratories, Astellas Pharma, Merck Serono, Millennium, the National Comprehensive Cancer Network, and Pfizer. Two of her co-authors have received honoraria from and/or served as consultants/advisers to AstraZeneca.