Chicago, IL—In men with metastatic prostate cancer, especially those with minimal disease spread, continuous rather than intermittent hormonal therapy should be considered the preferred therapy, according to the results of a large multicenter phase 3 international trial.
In these men, the difference in median survival favoring continuous therapy was approximately 2 years, said lead investigator Maha H. Hussain, MD, Professor of Medicine and Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, who presented the data at the 2012 meeting of the American Society of Clinical Oncology.
Continuous androgen deprivation therapy has been the standard of care for men with metastatic hormone-sensitive prostate cancer. In an effort to curb side effects from hormone therapy, such as loss of libido, weight gain, loss of muscle, and hot flashes, some oncologists have used intermittent hormone therapy with the belief that efficacy would not be affected.
Early clinical trials showed that intermittent therapy was feasible and may be associated with an improvement in quality of life. Based on these trials, there was broad acceptanceof intermittent therapy by patients, physicians, and insurers.
But the present study’s findings “clearly demonstrate that intermittent hormonal therapy is not safe for all patients with metastatic prostate cancer,” said Dr Hussain.
She noted that these data are practice changing. “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 pointed out.
The study, which was sponsored by the National Cancer Institute, included 1535 patients with newly diagnosed hormone-sensitive metastatic prostate cancer whose serum prostate-specific antigen level declined to ≤4 ng/mL after 7 months of continuous hormonal therapy with goserelin acetate in combination with bicalutamide. After stratifying them by disease extent, the patients were randomly assigned to receive intermittent hormonal therapy or continuous hormonal therapy.
The median age of the patients was 70 years. Approximately 50% had extensive disease, and 50% had minimal disease.
After a median follow-up of 9.2 years, median overall survival (OS) 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. This HR did not meet the prespecified definition for noninferiority, because the upper confidence interval for the relative increase in the risk of death exceeded 20% (the trial was designed to show whether intermittent therapy was noninferior to continuous therapy). In the arm receiving continuous therapy, 42% of patients were still alive at 7 years compared with 38% of the arm randomized to intermittent therapy.
For men with minimal disease spread, the difference in survival between the 2 groups was even greater. In this subset, median OS was 5.2 years in those receiving 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 noninferiority.
Among men with more extensive disease spread, median survival was similar in the 2 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.
According to Bruce J. Roth, MD, Professor of Medicine in the Division of Oncology at Washington University, St Louis, “prior underpowered studies suggested that there was no downside to intermittent therapy. This study demonstrates for the first time that there is a price to pay.” He noted that patients with minimal disease are the ones who have been most likely to receive intermittent therapy.