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. 2024 Jan 30;73(2):38.
doi: 10.1007/s00262-023-03621-1.

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

Takafumi Yanagisawa #  1   2 , Keiichiro Mori #  3   4 , Akihiro Matsukawa  1   2 , Tatsushi Kawada  1   5 , Satoshi Katayama  1   5 , Kensuke Bekku  1   5 , Ekaterina Laukhtina  1   6 , Pawel Rajwa  1   7 , Fahad Quhal  1   8 , Benjamin Pradere  1   9 , Wataru Fukuokaya  2 , Kosuke Iwatani  2 , Masaya Murakami  2 , Karim Bensalah  10 , Viktor Grünwald  11 , Manuela Schmidinger  1 , Shahrokh F Shariat  1   12   13   14   15   16 , Takahiro Kimura  2
Affiliations

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

Takafumi Yanagisawa et al. Cancer Immunol Immunother. .

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.

Keywords: Immune checkpoint inhibitors; Metastasis; Network meta-analysis; Renal cell carcinoma.

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Conflict of interest statement

Takahiro Kimura is a paid consultant/advisor for Astellas, Bayer, Janssen, and Sanofi. Shahrokh F. Shariat received honoraria from Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, and Takeda. Further, they are involved in a consulting or advisory role with Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, and Takeda and with the Speakers Bureau of Astellas, Astra Zeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, and Takeda. Manuela Schmidinger received honoraria for lectures to the advisory boards from Ipsen, Exelixis, BMS, MSD, Merck, EUSA, Eisai, Astellas, and Janssen. The other authors declare no conflicts of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
Forest plots showing the results of NMA among the overall population for OS, PFS, ORR, and CR in mRCC patients treated with first-line ICI-based combination therapy
Fig. 2
Fig. 2
Forest plots showing the results of NMAs for OS, PFS, ORR, and CR in mRCC patients with intermediate/poor risk treated with first-line ICI-based combination therapy
See this image and copyright information in PMC

References

    1. Ljungberg B, Albiges L, Abu-Ghanem Y, Bedke J, Capitanio U, Dabestani S, et al. European association of urology guidelines on renal cell carcinoma: the 2022 update. Eur Urol. 2022;82:399–410. doi: 10.1016/j.eururo.2022.03.006. - DOI - PubMed
    1. Motzer RJ, Jonasch E, Agarwal N, Alva A, Baine M, Beckermann K, et al. Kidney cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw JNCCN. 2022;20:71–90. doi: 10.6004/jnccn.2022.0001. - DOI - PMC - PubMed
    1. Lombardi P, Filetti M, Falcone R, Di Bidino R, Iacovelli R, Ciccarese C, et al. New first-line immunotherapy-based combinations for metastatic renal cell carcinoma: a systematic review and network meta-analysis. Cancer Treat Rev. 2022;106:102377. doi: 10.1016/j.ctrv.2022.102377. - DOI - PubMed
    1. Mori K, Mostafaei H, Miura N, Karakiewicz PI, Luzzago S, Schmidinger M, et al. Systemic therapy for metastatic renal cell carcinoma in the first-line setting: a systematic review and network meta-analysis. Cancer Immunol Immunother CII. 2021;70:265–273. doi: 10.1007/s00262-020-02684-8. - DOI - PMC - PubMed
    1. Quhal F, Mori K, Bruchbacher A, Resch I, Mostafaei H, Pradere B, et al. First-line immunotherapy-based combinations for metastatic renal cell carcinoma: a systematic review and network meta-analysis. Eur Urol Oncol. 2021;4:755–765. doi: 10.1016/j.euo.2021.03.001. - DOI - PubMed

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