TY - JOUR
T1 - Clinical Development of Darolutamide
T2 - A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer
AU - Fizazi, Karim
AU - Smith, Matthew R.
AU - Tombal, Bertrand
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths among men. Androgen receptor (AR) signaling plays a key role in PC tumor growth and progression, with androgens stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is characterized by increasing levels of prostate-specific antigen or radiographic progression despite androgen-deprivation therapy (ADT). In most patients, castration resistance results from aberrations in AR or the AR signaling pathway. Up to one-third of patients with localized high-risk PC will have disease progression on local therapy and develop CRPC. This review summarizes the key clinical data, including ongoing trials, for hormonal therapies in CRPC and provides an overview of the clinical development of darolutamide, a novel, nonsteroidal AR antagonist currently in phase III development for the treatment of nonmetastatic CRPC and metastatic hormone-sensitive PC. In phase I/II trials, darolutamide has demonstrated a favorable safety profile, antitumor activity, and significant decreases in prostate-specific antigen in patients with metastatic CRPC. In the phase III ARAMIS (NCT02200614; A Multinational, Randomized, Double-Blind, Placebo-Controlled, Phase III Efficacy and Safety Study of Darolutamide [ODM-201] in Men With High-Risk Non-metastatic Castration-Resistant Prostate Cancer) study, metastasis-free survival is being evaluated in men with nonmetastatic CRPC who will receive ADT in combination with darolutamide or placebo. The ARASENS (NCT02799602; A Randomized, Double-Blind, Placebo Controlled Phase III Study of Darolutamide [ODM-201] Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer) study is a placebo-controlled trial assessing whether the addition of darolutamide to ADT and docetaxel significantly prolongs overall survival in men with metastatic hormone-sensitive PC.
AB - Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths among men. Androgen receptor (AR) signaling plays a key role in PC tumor growth and progression, with androgens stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is characterized by increasing levels of prostate-specific antigen or radiographic progression despite androgen-deprivation therapy (ADT). In most patients, castration resistance results from aberrations in AR or the AR signaling pathway. Up to one-third of patients with localized high-risk PC will have disease progression on local therapy and develop CRPC. This review summarizes the key clinical data, including ongoing trials, for hormonal therapies in CRPC and provides an overview of the clinical development of darolutamide, a novel, nonsteroidal AR antagonist currently in phase III development for the treatment of nonmetastatic CRPC and metastatic hormone-sensitive PC. In phase I/II trials, darolutamide has demonstrated a favorable safety profile, antitumor activity, and significant decreases in prostate-specific antigen in patients with metastatic CRPC. In the phase III ARAMIS (NCT02200614; A Multinational, Randomized, Double-Blind, Placebo-Controlled, Phase III Efficacy and Safety Study of Darolutamide [ODM-201] in Men With High-Risk Non-metastatic Castration-Resistant Prostate Cancer) study, metastasis-free survival is being evaluated in men with nonmetastatic CRPC who will receive ADT in combination with darolutamide or placebo. The ARASENS (NCT02799602; A Randomized, Double-Blind, Placebo Controlled Phase III Study of Darolutamide [ODM-201] Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer) study is a placebo-controlled trial assessing whether the addition of darolutamide to ADT and docetaxel significantly prolongs overall survival in men with metastatic hormone-sensitive PC.
KW - ARAMIS
KW - ARASENS
KW - Androgen deprivation therapy
KW - Darolutamide
KW - Nonsteroidal
KW - ODM-201
UR - http://www.scopus.com/inward/record.url?scp=85052933660&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2018.07.017
DO - 10.1016/j.clgc.2018.07.017
M3 - Review article
C2 - 30197098
AN - SCOPUS:85052933660
SN - 1558-7673
VL - 16
SP - 332
EP - 340
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 5
ER -