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 Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
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.