A new meta-analysis suggests that survival outcomes are similar with intermittent and continuous androgen deprivation therapy, and that intermittent therapy may improve some quality-of-life criteria.
Continuous androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but a new meta-analysis suggests that overall survival outcomes between intermittent and continuous ADT are similar. The study also found that physical and sexual function was better among men who received intermittent ADT.
The research is published in JAMA Oncology.
There was no statistical difference between the two dosing schedules for overall survival (hazard ratio [HR], 1.02), cancer-specific survival (HR, 1.02), and progression-free survival (HR, 0.94).
There was also no difference in time to castration resistance. Of four trials that evaluated this endpoint, two trials showed a statistically significant difference favoring intermittent therapy; the difference was not significant in the two other trials. No differences in adverse events were found in the meta-analysis of twelve clinical trials, although not all trials systematically evaluated drug-related safety.
Sindy Magnan, MD, of the division of radiation oncology at the UniversitÃ© Laval in Quebec, Canada, and colleagues compiled data from 15 randomized clinical trials that included a total of 6,856 patients. All trial results were previously published between 2000 and 2013. A total of eight, five, and four trials were included in the overall survival, cancer-specific survival, and progression-free survival, respectively. The average age of trial participants was 70. The comprehensive analysis included three recent trials that compared the two ADT approaches.[1-3]
Two of the trials reported better quality of life with intermittent therapy while three trials showed no difference between intermittent and continuous therapy. Seven additional trials also reported better quality-of-life factors, namely, physical and sexual function, with intermittent ADT.
Limitations of the analysis include limitations of the available data for each study, only a descriptive reporting of quality-of-life data, “as well as a high risk of bias and the low methodological quality of the included trials,” wrote the study authors.
“One clear output from this meta-analysis is documentation of the vast variability of both the quality of the trials and the patient populations studied,” wrote Christopher J. Sweeney, MBBS, a medical oncologist at the Dana-Farber Cancer Institute in Boston, in an accompanying commentary.
While the authors based their conclusions on sound statistical analyses of pooled patient populations, Sweeney proposed that large population studies are not always relevant to individual patient care because there is “clinical uncertainty in the data,” and presented case scenarios that argue his point.
“In the metastatic setting, I propose that when a patient is not on a protocol, it is very reasonable to exercise clinical judgment whether to use intermittent ADT based on an individual patient’s response to therapy, adverse event profile, and risk of death from a competing comorbidity,” Sweeney concluded.
1. Crook JM, O’Callaghan CJ, Duncan G, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012;367:895–903.
2. Hussain M, Tangen CM, Berry DL, et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013;368:1314–1325.
3. Calais da Silva F, Calais da Silva FM, GonÃ§alves F, et al. Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: results from a randomised phase 3 study by the South European Uroncological Group. Eur Urol. 2014;66:232–239.