Triplet therapy for metastatic castration-sensitive prostate cancer: Rationale and clinical evidence.

Autor: Suzuki H; Department of Urology, Toho University Sakura Medical Center, Chiba, Japan., Akamatsu S; Department of Urology, Nagoya University, Nagoya, Japan., Shiota M; Department of Urology, Kyushu University, Fukuoka, Japan., Kakiuchi H; Oncology Medical Affairs, Medical Affairs and Pharmacovigilance, Bayer Yakuhin Ltd., Osaka, Japan., Kimura T; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Jazyk: angličtina
Zdroj: International journal of urology : official journal of the Japanese Urological Association [Int J Urol] 2024 Dec 09. Date of Electronic Publication: 2024 Dec 09.
DOI: 10.1111/iju.15647
Abstrakt: Prostate cancer (PC) growth is hormone-dependent and it frequently develops distant metastases as disease progresses. Patients with metastatic castration-sensitive prostate cancer (mCSPC) initially respond to androgen deprivation therapy (ADT) but eventually become refractory and develop metastatic castration-resistant prostate cancer (mCRPC). Castration-resistance is associated with high lethality and metastases confer poor prognosis, therefore unmet needs in treatment for mCSPC remain high. So far, improvements in survival in mCSPC have been achieved by doublet combination therapy such as docetaxel or an androgen-receptor signaling inhibitor (ARSI) in addition to ADT. Further, recent phase 3 trials have shown that triplet therapy-a combination of ARSI, docetaxel, and ADT improves prognosis compared with docetaxel plus ADT in mCSPC. PC tumors manifest intra- and inter-tumoral heterogeneity at both the genetic and phenotypic level. As heterogeneity increases during sequential treatment and disease progression, it is reasonable to initiate combination therapy using drugs with different mechanisms of action early in the course of disease, such as mCSPC. Previous research about tumor heterogeneity and drug resistant mechanism support this rationale, as well as preclinical studies and real-world data provide the scientific evidence of benefit by combining ARSI and docetaxel. Here, we review the rationale and clinical evidence for triplet therapy in patients with mCSPC.
(© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)
Databáze: MEDLINE
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