720PD - Long term efficacy and QOL data of chemohormonal therapy (C-HT) in low and high volume hormone naïve metastatic prostate cancer (PrCa): E3805 CHAAR...

Date 09 October 2016
Event ESMO 2016 Congress
Session Genitourinary tumours, prostate
Topics Cytotoxic agents
Prostate Cancer
Therapy
Biological therapy
Presenter Christopher Sweeney
Citation Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372
Authors C. Sweeney1, Y. Chen2, G. Liu3, M. Carducci4, D. Jarrard3, M. Eisenberger4, Y. Wong5, L. Patrick-Miller6, N. Hahn4, M. Kohli7, M. Conney8, R. Dreicer9, N.J. Vogelzang10, J. Picus11, D. Shevrin12, M. Hussain13, J. Garcia14, R. Dipaola15
  • 1Lank Center For Genitourinary Oncology, Dana Farber Cancer Institute, 02115 - Boston/US
  • 2Biostastictics, Dana-Farber Cancer Institute, 02446 - Boston/US
  • 3Oncology, UW Carbone Cancer Center, Madison/US
  • 4Oncology, Johns Hopkins Hospital, 21231 - Baltimore/US
  • 5Medical Oncology, Fox Chase Cancer Center, 19111 - Philadelphia/US
  • 6Medical Oncology, The University of Chicago Medical Centre, Chicago/US
  • 7Medical Oncology, Mayo Clinic, Rochester/US
  • 8Medical Oncology, University Hospitals Case Medical Center,, Cleveland/US
  • 9Medical Oncology, University of Virginia, Charlottesville/US
  • 10Medical Oncology, US Oncology Research c/o Comprehensive Cancer Crts of NV, Las Vegas/US
  • 11Medical Oncology, Washington University School of Medicine, 63110 - St Louis/US
  • 12Medical Oncology, NorthShore University HealthSystem, Chicago/US
  • 13Medical Oncology, University of Michigan, Ann Arbor/US
  • 14Medical Oncology, Cleveland Clinic Foundation, Cleveland/US
  • 15Medical Oncology, University of Kentucky, Lexington/US

Abstract

Background

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

Methods

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).

Results

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)

Conclusions

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

NCT00309985

Legal entity responsible for the study

NCI

Funding

NCI

Disclosure

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.