Early analyses revealed significant increase in overall survival (OS) for patients with a higher burden of disease with early docetaxel (D) plus androgen deprivation therapy (ADT) over ADT alone. Patients with low volume disease have a more favorable natural history with ADT alone and the benefit of early D for this distinct subset requires longer follow-up
790 men were accrued from 7/28/06 to 11/21/2012 and randomized to ADT alone or ADT + D at 75mg/m2 every 3 weeks for 6 cycles within 4 mos of ADT. Patients were prospectively stratified into high volume (HV) vs. low volume (LV) disease (HV: visceral metastases and/or 4 or more bone metastases with at least one outside of the vertebral column and pelvis).
As of April 23, 2016, the median follow-up was 53.7 months and there were 299 deaths of 513 HV pts and 100 deaths of the 277 LV pts. The overall median OS was 57.6 mos for ADT + D [95% CI: (52.0, 63.9)] and 47.2 (41.8, 52.8) for ADT alone HR: 0.73 (0.59, 0.89), p = 0.0018 (stratified log rank). Deaths and distribution of OS by arm and volume of disease are in Table 1. The evaluation of outcome by disease volume interaction with treatments revealed a p-value of 0.029 indicating the impact of early docetaxel differed between the HV and LV pts. The burden of cancer and therapy was assessed by FACT-P score and notable findings were (i) HV pts had lower baseline QOL than LV pts, (ii) there was a decline in QOL from baseline to 3 months in ADT + D LV ps and (iii) the lowest FACT-P score at 12 months was in ADT alone HV pts (see Table).
|Survival||ADT + D||ADT||p-value||HR (95%CI*)|
|LV Deaths / N (%)||51/134 (38.1%)||49/143 (34.3%)|
|LV Median OS mos*||63.5 (58.3, 78.5)||NR (59.8, - )||0.86||1.04 (0.70, 1.55)|
|HV Deaths/ N (%)||137/263 (52.1%)||162/250 (64.8%)|
|HV Median OS mos*||51.2 (45.2, 58.1)||34.4 (30.1, 42.1)|
The clinical benefit of ADT + D is limited to pts with a higher burden of metastatic prostate. Partial Support and drug supply by Sanofi.
Clinical trial identification
Legal entity responsible for the study
C. Sweeney: Grant support from the NCI, personal fees from Sanofi, Janssen, Astellas, Bayer, and Genentech. G. Liu: Dr. Liu reports grant support from the University of Wisconsin Carbone Cancer Center during the conduct of the study. M. Carducci: Dr. Carducci reports personal fees from Sanofi, Amgen, Astellas, and Medivation outside the submitted work. M. Eisenberger: Dr. Eisenberger reports personal fees from Sanofi outside the submitted work. Y-N. Wong: Dr. Wong reports other support from Sanofi during the conduct of the study; grant support from Pfizer, Medivation, Millennium, and other support from eviti outside the submitted work. N. Hahn: Grant support from Sanofi-Aventis and from Dendreon, grant support and personal fees from OncoGeneX, grant and non-financial support from Millennium, and personal fees from Medivation and Sanofi-Aventis outside the submitted work.
R. Dreicer: Dr. Dreicer reports personal fees from Millennium, Medivation, Astellas, Bind Pharmaceuticals, Genentech, Roche, and Dendreon outside the submitted work.
J. Picus: Dr. Picus reports grant support from the National Cancer Institute during the conduct of the study.
M. Hussain: Dr. Hussain reports grant support from the SWOG during the conduct of the study
J. Garcia: Dr. Garcia reports grant support and personal fees from Astellas and Bayer, and personal fees from Sanofi outside the submitted work.
R. Dipaola: Dr. DiPaola reports other support from Sanofi-Aventis during the conduct of the study
All other authors have declared no conflicts of interest.