805TiP - Randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate cance...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Surgery and/or Radiotherapy of Cancer
Presenter Scott Williams
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors S. Williams1, I.D. Davis2, C. Sweeney3, M. Stockler4, A. Martin4, A.P. Long4, S. Yip5, X. Coskinas4, P. Nguyen6
  • 1Radiation Oncology, Peter MacCallum Cancer Centre, 8006 - Melbourne/AU
  • 2Eastern Health Clinical School, Monash University, 3128 - Melbourne/AU
  • 3Lank Center For Genitourinary Oncology, Dana Farber Cancer Institute, 02115 - Boston/US
  • 4Nhmrc Clinical Trials Centre, University of Sydney, Sydney/AU
  • 5Nhmrc Clinical Trials Centre, University of Sydney, 2050 - Sydney/AU
  • 6Department Of Radiation Oncology, Dana Farber Cancer Institute, Boston/US

Abstract

Background

Background: Adjuvant androgen deprivation therapy (ADT) including a luteinising hormone releasing hormone analogue (LHRHA) is standard of care given before during and after radiotherapy for localised prostate cancer (PC) at high risk of recurrence. Enzalutamide is a new second generation androgen receptor (AR) inhibitor that is more potent and binds with a higher affinity to the AR than conventional non-steroidal anti-androgens (NSAA) and improves survival in metastatic castration-resistant PC. We hypothesise that the incorporation of enzalutamide in adjuvant ADT, given before, during and after radiation therapy for localised PC at high risk of recurrence, will further improve outcomes. Aim: To determine the effectiveness of enzalutamide as part of adjuvant ADT with a LHRHA in men planned for radiotherapy for localised PC at high risk of recurrence.

Trial design

Open label, randomised, stratified, 2-arm, phase 3 intergroup trial Eligibility: Localised PC, high risk of recurrence, suitable for EBRT with curative intent Stratification: Gleason 8-10, T3-4, PSA >20, study site Endpoints: Overall survival (Primary), Cause-specific survival, PSA PFS, Clinical PFS, HRQOL, Adverse events, ICER Accrual: 800 participants. 2 yrs accrual + 5.5 years minimum f/up. 80% power to detect a 33% reduction in the hazard of death assuming a 5-year survival rate of 76% amongst controls. Participants will be randomised 1:1 to enzalutamisde 160mg daily for 24 months versus conventional NSAA for first 6 months. Background treatment for all participants: LHRHA for 24 months and EBRT (78Gy/39F) starting after week 16. Study assessments are at baseline, weeks 4, 12, 16, 20 and 24, then 3-4 monthly until year 5, 6-monthly until year 7, then annually. Imaging with CT/MRI and bone scan at baseline and then as clinically indicated. Tertiary correlative objectives include the identification of prognostic / predictive biomarkers from archival tumour tissue, and from fasting bloods collected at baseline, 24 weeks, 5 years, and first evidence of progression. Email: enzarad@ctc.usyd.edu.au Website: http://www.anzup.org.au/

Disclosure

C. Sweeney: Consulting with honoraria to declare with Asetallas, Janssen and Sanofi; P. Nguyen: Consulted for Medivation (<$10,000) in Sept 2014. All other authors have declared no conflicts of interest.