TY - JOUR
T1 - Darolutamide for castration-resistant prostate cancer
AU - Bastos, Diogo A.
AU - Antonarakis, Emmanuel S.
N1 - Funding Information:
ESA has received funding from NIH grants R01 CA185297 and P30 CA006973, and DOD grant W81XWH-16-PCRP-CCRSA.
Publisher Copyright:
© 2019 Bastos and Antonarakis.
PY - 2019
Y1 - 2019
N2 - The treatment landscape of advanced prostate cancer continues to evolve rapidly, with newer and more active drugs being used in earlier phases of the disease based on improved overall survival. After adoption of docetaxel for metastatic castration-sensitive disease, large trials with next-generation androgen receptor-signaling inhibitors (abiraterone, enzalutamide and apalutamide) have demonstrate significant improvements in survival and important secondary endpoints. For non-metastatic castration-resistant prostate cancer, recent phase III placebo-controlled trials with enzalutamide, apalutamide and darolutamide all demonstrated benefits in improving metastasis-free survival. This review aims to summarize the clinical development of darolutamide, a novel next-generation androgen receptor antagonist, including preclinical data, clinical studies and the potential of darolutamide for the treatment of advanced prostate cancer. To date, darolutamide efficacy and tolerability has been demonstrated in the ARAMIS trial, which demonstrated an improvement in metastasis-free survival compared to placebo for non-metastatic castration-resistant prostate cancer patients with a rapid PSA doubling time. Ongoing studies will further evaluate the role of darolutamide in metastatic castration-sensitive prostate cancer in combination with docetaxel (ARASENS trial) and also in other stages of the disease.
AB - The treatment landscape of advanced prostate cancer continues to evolve rapidly, with newer and more active drugs being used in earlier phases of the disease based on improved overall survival. After adoption of docetaxel for metastatic castration-sensitive disease, large trials with next-generation androgen receptor-signaling inhibitors (abiraterone, enzalutamide and apalutamide) have demonstrate significant improvements in survival and important secondary endpoints. For non-metastatic castration-resistant prostate cancer, recent phase III placebo-controlled trials with enzalutamide, apalutamide and darolutamide all demonstrated benefits in improving metastasis-free survival. This review aims to summarize the clinical development of darolutamide, a novel next-generation androgen receptor antagonist, including preclinical data, clinical studies and the potential of darolutamide for the treatment of advanced prostate cancer. To date, darolutamide efficacy and tolerability has been demonstrated in the ARAMIS trial, which demonstrated an improvement in metastasis-free survival compared to placebo for non-metastatic castration-resistant prostate cancer patients with a rapid PSA doubling time. Ongoing studies will further evaluate the role of darolutamide in metastatic castration-sensitive prostate cancer in combination with docetaxel (ARASENS trial) and also in other stages of the disease.
KW - Androgen receptor antagonist
KW - Castration-resistant
KW - Darolutamide
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85074319881&partnerID=8YFLogxK
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U2 - 10.2147/OTT.S197244
DO - 10.2147/OTT.S197244
M3 - Review article
C2 - 31695432
AN - SCOPUS:85074319881
SN - 1178-6930
VL - 12
SP - 8769
EP - 8777
JO - OncoTargets and Therapy
JF - OncoTargets and Therapy
ER -