Intermittent androgen deprivation is not inferior to continuous therapy in prostate cancer patients, when looking at overall survival, and can be considered an alternative option for patients with recurrent or metastatic disease, according to a new meta-analysis published online Sept. 17 in JAMA Oncology.
Additionally, even though there were no major differences in quality of life observed between groups, some domains seemed to be improved with intermittent therapy.
But the researchers emphasize that it is not yet time to completely give up continuous therapy. “The high risk of bias observed in some trials, the unclear optimal approach to the duration of treatment and off-treatment periods and criteria on which it should be based, and the unknown magnitude of effect according to the disease stage warrant further research before it becomes the mandatory standard of care,” wrote Dr. Sindy Magnan, Université Laval, Quebec City, and colleagues. (JAMA Oncol. 2015. doi: 10.1001/jamaoncol.2015.2895).
Even though intermittent androgen deprivation appears to be an attractive option in this population, evidence for its safety and efficacy is rather limited, and because of that, its use remains somewhat controversial. Recommendations in current guidelines are also variable and not consistent.
However, the importance of assessing this treatment modality is growing, the authors pointed out, given the increase in the number of clinical trials and use of intermittent androgen deprivation therapy (ADT) in clinical practice, and was the impetus for conducting this systematic review and meta-analysis.
A total of 22 articles from 15 trials, for a total of 6,856 patients met their inclusion criteria. All papers were published between 2000 and 2013, and all but one study had an unclear or high risk of bias.
There were only six trials that provided survival data and hazard rations, and two others provided enough information to calculate the hazard ratios. There was no difference between intermittent and continuous therapy based on pooled results of those eight trials (5,352 patients, hazard ratio for death, 1.02; 95% confidence interval, 0.93-1.11; I2 = 23%).
No significant differences were observed between the two treatment groups with respect to cancer-specific survival based on pooled results from five trials (3,613 patients, HR for death, 1.02; 95% CI, 0.87-1.19; I2 = 14%). These results were also consistent across all subgroup and sensitivity analyses.
The same was true for progression-free survival, with no significant differences observed between groups (HR, 0.94; 95% CI, 0.84-1.05; four trials, 1,774 patients).
For quality of life, two trials reported that it was improved with intermittent therapy, while three trials did not observe any difference between the two treatment methods. The other seven trials showed that quality of life was increased with intermittent therapy but only in certain domains, with the most frequently detected differences relating to physical and sexual functioning.
Dr. Magnan is a recipient of a Resident Physician Health Research Career Training Grant from the Fonds de Recherche du Quebec–Santé (FRQS). Dr. Fradet and Dr. Turgeon are recipients of a Clinician-Scientist Award from the FRQS. Dr. Vigneault has received honoraria for consultation for Abvie, Sanofie, Jansen, Astellas, Peladin, and Amgen. None of the other authors have reported disclosures.