769TiP - ATLAS: A phase 3 trial evaluating the efficacy of apalutamide (ARN-509) in patients with high-risk localized or locally advanced prostate cancer re...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Cytotoxic agents
Prostate Cancer
Therapy
Biological therapy
Presenter Alberto Bossi
Citation Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372
Authors A. Bossi1, D. Dearnaley2, M. McKenzie3, E. Baskin-Bey4, R. Tyler4, B.F. Tombal5, S.J. Freedland6, M. Roach III7, A. Widmark8, A.P. Dicker9, T. Wiegel10, N. Shore11, M. Smith12, M. Yu4, T. Kheoh13, S. Thomas14, H.M. Sandler15
  • 1Radiation Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 2Academic Radiotherapy, The Institute of Cancer Research and The Royal Marsden Hospital, SW3 6JJ - London/GB
  • 3Medical Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 4Wc Clinical Oncology, Janssen Research & Development, Los Angeles/US
  • 5Urology, Cliniques Universitaires St. Luc, 12000 - Brussels/BE
  • 6Surgery, Cedars-Sinai Medical Center, Los Angeles/US
  • 7Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco/US
  • 8Radiation Sciences, Umea University, Umea/SE
  • 9Radiation Oncology, Thomas Jefferson University, Philadelphia/US
  • 10Radiation Oncology, Ulm Medical University, Ulm/DE
  • 11Urology, Carolina Urologic Research Center, 29572 - Myrtle Beach/US
  • 12Hematology-oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 02114 - Boston/US
  • 13Clinical Biostatistics, Janssen Research & Development, San Diego/US
  • 14Oncology Translational Research, Janssen Pharmaceuticals, Spring House/US
  • 15Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles/US

Abstract

Background

Current management of high-risk localized or locally advanced prostate cancer includes 2 to 3 years of androgen deprivation therapy (ADT; gonadotropin-releasing hormone agonist [GnRHa]) along with primary radiation therapy (RT). Despite aggressive treatment, there is still a higher risk of metastasis and prostate cancer–related death in these patients. We hypothesize that the addition of the selective androgen receptor antagonist apalutamide to GnRHa will improve metastasis-free survival in high-risk patients receiving primary RT.

Trial design

This is a randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy of apalutamide in patients with high-risk localized or locally advanced prostate cancer (Gleason score of ≥ 8 and ≥ cT2c or a Gleason score of ≥ 7 and prostate-specific antigen ≥ 20 ng/mL and ≥ cT2c) receiving primary RT. Stratification: Gleason score (7 or ≥ 8), N0 or N1, brachytherapy boost (yes or no), and region (North American, European Union, or other). All patients will receive active treatment with GnRHa throughout the 30 (28-day) treatment cycles. Randomization: 1:1 to apalutamide or control. Neoadjuvant/concurrent (cycles 1-4) to RT (74-80 Gy): apalutamide 240 mg/d vs bicalutamide 50 mg/d; adjuvant to RT (cycles 5-30): apalutamide 240 mg/d vs placebo. Primary end point: metastasis-free survival. Secondary end points: time to local-regional recurrence, time to castration-resistant disease, time to distant metastasis, and overall survival. Imaging and bone scan will be conducted at baseline and then every 6 months following biochemical failure until documented distant metastasis by blinded independent central review or death. Approximately 1500 patients will be accrued to provide appropriate statistical power to detect the hypothesized risk reduction (25%) in metastasis or death. An independent data monitoring committee is commissioned to review trial data. Approximately 300 study sites are planned in 20 countries across North America, Latin America, Europe, and Asia. Sites in 11 countries are currently recruiting.

Clinical trial identification

NCT02531516.

Legal entity responsible for the study

Janssen Research & Development

Funding

Janssen Research & Development

Disclosure

D. Dearnaley: Consulting or Advisory Role - Cadence Research and Consulting, FirstWord, Janssen Pharmaceuticals, Janssen Pharmaceuticals, Sandoz, and Takeda; Travel, Accommodations, Expenses - Takeda; Expert Testimony - Vitality Life; Honoraria - Takeda.

M. McKenzie: Honoraria - Amgen and Bayer; Consulting or Advisory Role - Johnson & Johnson.

E. Baskin-Bey: Employee of Janssen Research & Development.

R. Tyler, T. Kheoh, S. Thomas: Employee of Janssen Research & Development and holds stock in Johnson & Johnson.

B. Tombal: Speaker and Investigator Fees - Janssen.

S.J. Freedland: Consulting or Advisory Role - Astellas Pharma, Dendreon, Janssen Biotech, MDxHealth, Medivation, and Sanofi; Speakers' Bureau - Dendreon; Travel, Accommodations, Expenses - Myriad Genetics and Sanofi.

A. Widmark: Employment - Sanofi; Honoraria - Astellas Pharma, Bayer, Janssen, and Sanofi; Consulting or Advisory Role - EXINI Diagnostics.

A.P. Dicker: Consulting or Advisory role - Glenview, Janssen, Merck, and Redhill.

T. Wiegel: Honoraria - Ferring, Hexal, Ipsen, and Siemens; Consulting or Advisory Role - Ferring and Ipsen.

N. Shore: Consulting or Advisory Role - Astellas, Bayer, Ferring, Janssen, Millennium, Pfizer, and Sanofi; Research Funding - Carolina Urologic Research Center; Travel, Accomodations, Expenses - Astellas, Bayer, Ferring, Janssen, Millennium, Pfizer, and Sanofi.

M. Smith: Consulting or Advisory Role - Astellas Pharma, Bayer, and Janssen Oncology.

M. Yu: Employee of Janssen Research & Development and holds stock in Johnson & Johnson.

H.M. Sandler: Consulting or Advisory Role - Medivation/Astellas, Blue Earth, Eviti, Ferring, Janssen Pharmaceuticals, and Sanofi; Honoraria - Varian Medical Systems.

All other authors have declared no conflicts of interest.