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Open Access 01-02-2024 | Axitinib | Review

Updated systematic review and network meta-analysis of first-line treatments for metastatic renal cell carcinoma with extended follow-up data

Authors: Takafumi Yanagisawa, Keiichiro Mori, Akihiro Matsukawa, Tatsushi Kawada, Satoshi Katayama, Kensuke Bekku, Ekaterina Laukhtina, Pawel Rajwa, Fahad Quhal, Benjamin Pradere, Wataru Fukuokaya, Kosuke Iwatani, Masaya Murakami, Karim Bensalah, Viktor Grünwald, Manuela Schmidinger, Shahrokh F. Shariat, Takahiro Kimura

Published in: Cancer Immunology, Immunotherapy | Issue 2/2024

Abstract

Immune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.

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Title: Updated systematic review and network meta-analysis of first-line treatments for metastatic renal cell carcinoma with extended follow-up data
Authors: Takafumi Yanagisawa
Keiichiro Mori
Akihiro Matsukawa
Tatsushi Kawada
Satoshi Katayama
Kensuke Bekku
Ekaterina Laukhtina
Pawel Rajwa
Fahad Quhal
Benjamin Pradere
Wataru Fukuokaya
Kosuke Iwatani
Masaya Murakami
Karim Bensalah
Viktor Grünwald
Manuela Schmidinger
Shahrokh F. Shariat
Takahiro Kimura
Publication date: 01-02-2024
Publisher: Springer Berlin Heidelberg
Keywords: Axitinib
Cabozantinib
Sunitinib
Checkpoint Inhibitors
Lenvatinib
Kidney Cancer
Kidney Cancer
Kidney Cancer
Tyrosine Kinase Inhibitors
Tyrosine Kinase Inhibitors
Metastasis
Published in: Cancer Immunology, Immunotherapy / Issue 2/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-023-03621-1

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