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.
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
Legal entity responsible for the study
Janssen Research & Development
Janssen Research & Development
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.