GPGU – NOTÍCIAS
ATLAS: A randomized, double-blind, placebo-controlled, phase 3 trial of apalutamide (ARN-509) in patients with high-risk localized or locally advanced prostate cancer receiving primary radiation therapy.
Howard M. Sandler, Michael R. McKenzie, Bertrand F. Tombal, Edwina Baskin-Bey, Stephen J. Freedland, Mack Roach, Anders Widmark, Alberto Bossi, Adam Dicker, Thomas Wiegel, Neal D. Shore, Matthew Raymond Smith, Margaret K. Yu, ThianKheoh, Shibu Thomas, David P. Dearnaley; Cedars-Sinai Medical Center, Los Angeles, CA; British Columbia Cancer Agency, Vancouver, BC, Canada; CliniquesUniversitaires Saint-Luc, Brussels, Belgium; Janssen Research & Development, Los Angeles, CA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; Umea University, Umea, Sweden; Institute Gustave Roussy, Villejuif, France; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; University Hospital Ulm, Ulm, Germany; Carolina Urologic Research Center, Myrtle Beach, SC; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Janssen Research & Development, San Diego, CA; Janssen Pharmaceuticals, Spring House, PA; The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom
Abstract:
Background: At present, high-risk localized and locally advanced prostate cancer (PC) patients receiving primary radiation therapy (RT) and long-term androgen deprivation therapy (ADT; gonadotropin-releasing hormone [GnRH] agonist +/- antiandrogen) have a high risk of metastases and PC-specific death. We hypothesize that the addition of apalutamide, a selective androgen receptor (AR) antagonist, to GnRH agonist will improve metastasis-free survival in high-risk patients treated with primary RT. Methods: This is a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of apalutamide in patients with high-risk localized or locally advanced PC (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 a GnRH agonist 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 with CT or MRI and bone scan will be conducted at baseline and then every 6 months following biochemical failure until documented distant metastasis by blinded-to-arm independent central review or death. Approximately 1500 patients will be accrued globally 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.