There is an increased focus on improving outcomes of prostate cancer (PC) patients (pts) by introducing treatments before castration resistance occurs. Results from CHAARTED (Sweeney NEJM. 2015) and STAMPEDE (James Lancet. 2015) demonstrate a survival advantage with ADT (gonadotropin-releasing hormone analog or surgical castration) in combination with docetaxel (DOC) for pts with metastatic PC, and practice guidelines recommend ADT + DOC for pts with metastatic disease. Inhibition of the androgen receptor (AR) in addition to ADT may provide more complete blockade of androgen signaling vs ADT alone. We hypothesize that apalutamide (APA), a selective AR antagonist, plus ADT will improve radiographic progression-free survival (rPFS) and overall survival (OS) compared with ADT alone, and have an acceptable safety profile in pts with mHSPC.
This is a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of APA + ADT in pts with Eastern Cooperative Oncology Group performance status ≤ 1 and mHSPC (metastatic disease documented by ≥ 1 bone lesions with or without visceral metastasis). Pts will be stratified by Gleason score (≤ 7 vs > 7), region (North America, European Union vs other), and prior DOC use (yes/no). Up to 6 cycles of DOC for mHSPC is allowed, with last dose within 2 mos of randomization. Up to 6 mos ADT for mHSPC is allowed prior to randomization. Approximately 1000 pts will be randomized (1:1) to APA (240 mg/d) + ADT or placebo + ADT in 28-day cycles. Co-primary end points: rPFS and OS. Secondary end points: time to pain progression, time to skeletal-related event, time to chronic opioid use, and time to initiation of cytotoxic chemotherapy. Samples for pharmacokinetics and biomarkers will be collected to correlate with clinical parameters. An independent data monitoring committee will review safety and efficacy data.
Clinical trial identification
Legal entity responsible for the study
Janssen Global Services, LLC
Janssen Global Services, LLC
K.N. Chi: Membership on an advisory board - Janssen; Research funding - Janssen
S. Chowdhury: Honoraria - Sanofi; Research funding – Sanofi.
P. Radziszewski: Consulting or Advisory role - Astellas Pharma and Pierre Fabre; Speakers Bureau - Astellas Pharma, GlaxoSmithKline, and Prizer; Research funding - Astellas Pharma, Allergan, and Pierre Fabre.
T. Lebret: Consulting or Advisory Role - Bayer, Janssen, and MSD; Speakers' Bureau - Janssen, Roche, and Ipsen; Research funding - Astellas; Travel, Accomodations, Expenses - Novartis and Astellas.
C. Sternberg: Honoraria - Astellas, Bayer, Janssen, BMS, Novartis, and Sanofi.
R.B. Sims, M. Yu, V. Naini, M. Darif: Employee of Janssen Research & Development and owns stock in Johnson & Johnson.
A.S. Merseburger: Honoraria - Janssen, Astellas, and Ipsen; Consulting or Advisory Role - Janssen, Astellas, and Ipsen; Speakers' Bureau - Janssen, Astellas, and Ipsen; Travel, Accomodations, Expenses - Janssen, Astellas, and Ipsen.
All other authors have declared no conflicts of interest.