Intermittent androgen deprivation therapy failed to improve survival rates or quality of life compared with continuous therapy in patients with metastatic hormone-sensitive prostate cancer, according to study results.
Data from an androgen-dependent tumor model indicated that if androgens were replaced before progression of the disease, the remaining stem cells could generate an androgen-dependent tumor that would be vulnerable to hormonal manipulation.
Although androgen-sensitive models have suggested that intermittent androgen deprivation is inferior to castration in preventing tumor growth, clinical trials involving androgen-dependent models indicated that intermittent androgen deprivation resulted in reinduction of apoptosis, nearly tripling the time to castration resistance.
To assess whether intermittent androgen deprivation is noninferior to continuous androgen deprivation regarding prostate cancer survival, Maha Hussain, MD, FACP, professor of medicine and urology at the University of Michigan Comprehensive Cancer Center and a HemOnc Today Editorial Board member, and colleagues randomly assigned 1,533 patients with metastatic hormone-sensitive prostate cancer to continuous androgen deprivation (n=765) or intermittent androgen deprivation (n=770).
The study cohort included patients with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a PSA level of 5 ng/mL or higher. Patients received a luteinizing hormone-releasing hormone analogue and an anti-androgen agent for 7 months.
In addition, the researchers randomly assigned patients in whom the PSA level fell to 4 ng/mL or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status and extent of disease.
Study results showed median survival was 5.8 years in the continuous therapy group and 5.1 years in the intermittent-therapy group (HR for mortality with intermittent therapy, 1.10; 90% CI, 0.99-1.23). This translates to a 7-month difference in median survival.
“While we could not conclude that intermittent therapy is statistically significantly inferior to continuous therapy, a 7-month difference in median survival and survival trends that favored continuous therapy in all subgroups is clinically relevant and important,” Hussain told HemOnc Today. “This should also be viewed in the context of lack of scientific evidence from other clinical trials of ‘true equivalence’ between these treatment approaches.”
The effect of intermittent therapy on quality of life was modest, Hussain said. The researchers found that intermittent therapy initially was associated with improved erectile function (P<.001) and mental health (P=.003), but those differences leveled off after a few months and were not sustained.
“Based on the results of this trial, continuous androgen deprivation remains the standard based on optimal survival outcomes,” Hussain said. “Patients interested in intermittent therapy should be counseled regarding the potential negative impact on survival.”
Maha Hussain, MD, FACP, can be reached at University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109; email: firstname.lastname@example.org.