804TiP - Randomised phase 3 trial of enzalutamide in first line androgen deprivation therapy for metastatic prostate cancer: ENZAMET (ANZUP 1304)

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Presenter Ian Davis
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors I.D. Davis1, M. Stockler2, A. Martin2, A. Long2, S. Yip3, X. Coskinas2, C. Sweeney4
  • 1Eastern Health Clinical School, Monash University, 3128 - Melbourne/AU
  • 2Nhmrc Clinical Trials Centre, University of Sydney, Sydney/AU
  • 3Nhmrc Clinical Trials Centre, University of Sydney, 2050 - Sydney/AU
  • 4Lank Center For Genitourinary Oncology, Dana Farber Cancer Institute, 02115 - Boston/US

Abstract

Background

Androgen deprivation therapy (ADT) with luteinising hormone releasing hormone analogue (LHRHA) or surgical castration alone, or combined with conventional non-steroidal anti-androgen (NSAA), is widely used as initial treatment for hormone-sensitive prostate cancer (PC). Meta-analysis of RCTs showed a 3% absolute improvement in 5 year survival with the addition of a conventional NSAA to a LHRHA or surgical castration. Residual, low level androgen receptor (AR) signalling, or agonist activity from conventional NSAA, may provide a stimulatory signal to hormone-sensitive PC cells. We hypothesize that early use of enzalutamide, a more potent and effective androgen receptor blocker, will reduce residual AR signalling, and improve survival. Aim: To determine the effectiveness of ADT + enzalutamide versus ADT + conventional NSAA, as first-line ADT for M1 PC.

Trial design

Open label, randomised, stratified 2-arm, multicentre, intergroup, phase 3 trial

Eligibility, stratification, endpoints and statistics
Eligibility Stratification Endpoints Statistics
Met PC Starting first line ADT Adequate organ function Volume of disease Antiresorptive therapy Comorbidities Study site Overall Survival (Primary) PSA PFS Clinical PFS HRQOL Adverse events ICER 1100 participants 2 yrs accrual 3.5 yrs min f/up 80% power to detect 25% reduction in HR of death from any cause

Participants randomised 1:1 to Enzalutamide 160mg daily or conventional NSAA daily until disease progression or prohibitive toxicity. All participants are treated with LHRHA or surgical castration. Assessments at baseline, day 29, week 12, and then every 12 weeks from randomisation until evidence of clinical progression. Imaging with CT scan and WBBS at baseline and evidence of PSA or clinical progression. Tertiary objectives are to identify prognostic / predictive biomarkers. Archival tumour tissue and fasting bloods at baseline, week 24, and 1st progression (PSA/clinical) will be collected. Email: enzamet@ctc.usyd.edu.au Website: http://www.anzup.org.au/

Disclosure

C. Sweeney: Consulting with honoraria to declare with Asetallas, Janssen and Sanofi. All other authors have declared no conflicts of interest.