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International journal of urology : official journal of the Japanese Urological Association
Mar, 2025;32 (3): 239-250.

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

Hiroyoshi Suzuki, Shusuke Akamatsu, Masaki Shiota, Haruka Kakiuchi, Takahiro Kimura
Author Information
  1. Hiroyoshi Suzuki: Department of Urology, Toho University Sakura Medical Center, Chiba, Japan. ORCID
  2. Shusuke Akamatsu: Department of Urology, Nagoya University, Nagoya, Japan.
  3. Masaki Shiota: Department of Urology, Kyushu University, Fukuoka, Japan. ORCID
  4. Haruka Kakiuchi: Oncology Medical Affairs, Medical Affairs and Pharmacovigilance, Bayer Yakuhin Ltd., Osaka, Japan.
  5. Takahiro Kimura: Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. ORCID
PMID: 39651632 DOI: 10.1111/iju.15647

Abstract

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.

Keywords

androgen receptor signaling inhibitor docetaxel metastatic castration���sensitive prostate cancer prostate cancer triplet therapy

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Grants

  1. /Bayer Yakuhin Ltd.

MeSH Term

Humans
Male
Prostatic Neoplasms, Castration-Resistant
Docetaxel
Antineoplastic Combined Chemotherapy Protocols
Androgen Antagonists
Androgen Receptor Antagonists
Neoplasm Metastasis
Disease Progression

Chemicals

Docetaxel
Androgen Antagonists
Androgen Receptor Antagonists
Journal Article Review

Word Cloud

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