In prior studies with men who have had a PSA recurrence after radiotherapy (RT), intermittent androgen suppression (IAS) has been suggested to improve quality of life (QoL) but effects on survival are unknown.
The researchers performed an inter-group randomized phase III trial, which compared IAS vs continuous androgen deprivation (CAD) to test overall survival (OS) differences between the two therapies.
All subjects had rising PSA greater than 3.0 ng/ml in a time period greater than1 year post RT, RT was either initial or salvage or for localized prostate cancer. The men could receive up to 1 year of neo/adjuvant androgen deprivation therapy (ADT) completed longer than 1 year prior.
Stratification factors were time since RT (> 1-3 vs > 3 years), initial PSA (>15 vs > 15), prior radical prostatectomy and prior ADT. IAS was delivered for 8 months in each cycle with restart when PSA reached >10 ng/ml off treatment.
Primary endpoint was overall survival (OS); secondary endpoints included time to hormone refractory state (HR), QoL, cholesterol/HDL/LDL, duration of treatment/non-treatment intervals, time to testosterone and potency recovery. The independent DSMC recommended halting the trial after a planned interim analysis demonstrated that a pre-specified stopping boundary for non-inferiority was crossed.
Results: 1,386 men were randomized to IAS (690) or CAD (696) arms. Arms were balanced for important baseline factors. Median follow up was 6.9 years.
1- IAS men completed a median of 2 x 8 month cycles (range: 1-9).
2- 524 deaths were observed (268 on IAS vs 256 on CAD).
3- Median OS was 8.8 vs 9.1 years on IAS and CAD arms, respectively (HR 1.02, 95%CI 0.86-1.21; p for non-inferiority [HR IAS vs CAD ? 1.25] = 0.009).
4- The IAS arm had more disease related (122 vs 97) and fewer unrelated (134 vs 146) deaths.
5- Time to HR was statistically significantly improved on the IAS arm (HR 0.80, 95%CI 0.67-0.98; p = 0.024).
6- IAS patients had reduced hot flashes, but otherwise there was no evidence of differences in side effects, including myocardial events or osteoporotic fractures.
Conclusions: In men with PSA recurrence after radio therapy, intermittent androgen suppression, given as described, is equal to CAD with respect to overall survival.
Meeting: 2011 Genitourinary Cancers Symposium
General Poster Session A: Prostate Cancer
General Session II: Prostate Cancer Therapy for Recurrent Disease
J Clin Oncol 29: 2011 (suppl 7; abstr 3)
Author(s):L. Klotz, C. J. O’Callaghan, K. Ding, D. P. Dearnaley, C. S. Higano, E. M. Horwitz, S. Malone, S. L. Goldenberg, M. K. Gospodarowicz, J. M. Crook; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; National Cancer Institute of Canada Clinical Trials Group, Kingston, ON, Canada; Institute of Cancer Research, Surrey, United Kingdom; University of Washington School of Medicine, Seattle, WA; Fox Chase Cancer Center, Philadelphia, PA; Ottawa Health Research Institute, Ottawa, ON, Canada; Vancouver Prostate Centre, Vancouver, BC, Canada; Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada; British Columbia Cancer Agency, Kelowna, BC, Canada