Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution

Kawashima, Atsunari; Ishizuya, Yu; Yamamoto, Yoshiyuki; Kato, Taigo; Hatano, Koji; Nonomura, Norio

doi:https://doi.org/10.1007/s10147-024-02526-y

Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution

Kawashima, Atsunari; Ishizuya, Yu; Yamamoto, Yoshiyuki et al.

International Journal of Clinical Oncology, 2024, 29(8), 1096-1104

Number of Access:1,118（2025-10-12 09:48 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97110

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Title	Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution
Creator	NRID 1000050746568 1000050746568 researchmap permalink akawashima akawashima Scopus Author ID 9846139400 9846139400 CreatorName Kawashima, Atsunari
	NRID 1000000783854 1000000783854 researchmap permalink okiishi okiishi CreatorName Ishizuya, Yu
	NRID 1000090759557 1000090759557 researchmap permalink yoshi229 yoshi229 ORCID 0000-0002-1271-3521 0000-0002-1271-3521 CreatorName Yamamoto, Yoshiyuki
	NRID 1000070648021 1000070648021 researchmap permalink taigokato taigokato Scopus Author ID 55414697500 55414697500 ORCID 0000-0002-8681-1407 0000-0002-8681-1407 CreatorName Kato, Taigo
	NRID 1000060762234 1000060762234 researchmap permalink koji_hatano koji_hatano Scopus Author ID 14627167600 14627167600 CreatorName Hatano, Koji
	NRID 1000030263263 1000030263263 researchmap permalink read0185096 read0185096 Scopus Author ID 7005880662 7005880662 CreatorName Nonomura, Norio
Subject	ADC
	Chemotherapy
	First line
	Immunotherapy
	Urothelial carcinoma
Description	The version of record of this article, first published in International Journal of Clinical Oncology, is available online at Publisher’s website: https://doi.org/10.1007/s10147-024-02526-y.
Abstract	Urothelial carcinoma presents significant treatment challenges, especially in advanced stages. Traditionally managed with platinum-based chemotherapy, the advent of immunotherapies, particularly immune checkpoint inhibitors, has revolutionized urothelial carcinoma treatment. This review explores the evolution of urothelial carcinoma management, focusing on the transition from immune checkpoint inhibitors monotherapy to innovative combination therapies. Pembrolizumab, following the KEYNOTE-045 trial, emerged as a pivotal ICI in pretreated metastatic urothelial carcinoma, outperforming traditional chemotherapy. However, limitations surfaced in untreated metastatic urothelial carcinoma patients, particularly in those with low PD-L1 expression, as evidenced by trials like IMvigor130 and KEYNOTE-361. These challenges led to the exploration of combination therapies, including immune checkpoint inhibitors with platinum-based chemotherapy, tyrosine kinase inhibitors, and antibody–drug conjugates. Notably, the CheckMate 901 trial demonstrated improved outcomes with a nivolumab–chemotherapy combination. A significant breakthrough was achieved with the combination of enfortumab vedotin, an antibody–drug conjugates, and pembrolizumab, setting a new standard in first-line treatment for locally advanced or metastatic urothelial carcinoma. Future directions involve further exploration of antibody–drug conjugates and immune checkpoint inhibitors, as seen in the TROPHY-U-01 and TROPiCS-4 trials. The review concludes that the locally advanced or metastatic urothelial carcinoma treatment landscape is rapidly evolving, with combination therapies offering promising avenues for improved patient outcomes, signaling a new era in urothelial carcinoma management.
Publisher	Springer
Source Title	International Journal of Clinical Oncology
Volume (Issue)	29(8)
Page	1096-1104
Date of Issued	2024-06-08
Language	English
Handle URL	https://hdl.handle.net/11094/97110
PISSN	13419625
eISSN	14377772
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s10147-024-02526-y
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	International Journal of Clinical Oncology. 2024, 29(8), p. 1096-1104
DC.title	Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution
DC.creator	Kawashima, Atsunari
	Ishizuya, Yu
	Yamamoto, Yoshiyuki
	Kato, Taigo
	Hatano, Koji
	Nonomura, Norio
DC.publisher	Springer
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-06-08
DC.identifier	https://doi.org/10.1007/s10147-024-02526-y
DC.subject	ADC
	Chemotherapy
	First line
	Immunotherapy
	Urothelial carcinoma
DC.description	The version of record of this article, first published in International Journal of Clinical Oncology, is available online at Publisher’s website: https://doi.org/10.1007/s10147-024-02526-y.
DCTERMS.abstract	Urothelial carcinoma presents significant treatment challenges, especially in advanced stages. Traditionally managed with platinum-based chemotherapy, the advent of immunotherapies, particularly immune checkpoint inhibitors, has revolutionized urothelial carcinoma treatment. This review explores the evolution of urothelial carcinoma management, focusing on the transition from immune checkpoint inhibitors monotherapy to innovative combination therapies. Pembrolizumab, following the KEYNOTE-045 trial, emerged as a pivotal ICI in pretreated metastatic urothelial carcinoma, outperforming traditional chemotherapy. However, limitations surfaced in untreated metastatic urothelial carcinoma patients, particularly in those with low PD-L1 expression, as evidenced by trials like IMvigor130 and KEYNOTE-361. These challenges led to the exploration of combination therapies, including immune checkpoint inhibitors with platinum-based chemotherapy, tyrosine kinase inhibitors, and antibody–drug conjugates. Notably, the CheckMate 901 trial demonstrated improved outcomes with a nivolumab–chemotherapy combination. A significant breakthrough was achieved with the combination of enfortumab vedotin, an antibody–drug conjugates, and pembrolizumab, setting a new standard in first-line treatment for locally advanced or metastatic urothelial carcinoma. Future directions involve further exploration of antibody–drug conjugates and immune checkpoint inhibitors, as seen in the TROPHY-U-01 and TROPiCS-4 trials. The review concludes that the locally advanced or metastatic urothelial carcinoma treatment landscape is rapidly evolving, with combination therapies offering promising avenues for improved patient outcomes, signaling a new era in urothelial carcinoma management.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	97110
citation_title	Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution
citation_author	Kawashima, Atsunari
	Ishizuya, Yu
	Yamamoto, Yoshiyuki
	Kato, Taigo
	Hatano, Koji
	Nonomura, Norio
citation_publisher	Springer
citation_language	English
citation_date	2024-06-08
citation_journal_title	International Journal of Clinical Oncology
citation_volume	29
citation_issue	8
citation_firstpage	1096
citation_lastpage	1104
citation_doi	https://doi.org/10.1007/s10147-024-02526-y
citation_public_url	https://hdl.handle.net/11094/97110

Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution

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