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First-line therapy for elderly patients with advanced renal cell carcinoma in the immuno-oncology era: a network meta-analysis

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Abstract

Background

Tyrosine kinase inhibitors (TKI) or immune checkpoint blockade (ICB), either alone or in combination, confers a significant overall survival (OS) benefit for metastatic RCC in the first-line setting. However, guidance for optimal treatment selection in elderly patients remains limited.

Methods

A database search was performed to identify eligible randomized controlled trials (RCTs) evaluating first-line regimens for patients with advanced RCC older than 65 years old. The primary outcomes were progression-free survival (PFS) and OS. Indirect comparisons of available regimens were estimated using a random-effects network meta-analysis.

Results

A total of 14 and five RCTs were eligible for PFS and OS analyses. Compared with sunitinib, pembrolizumab plus axitinib (HR 0.68, 95% CI 0.48–0.97) and pembrolizumab plus lenvatinib (HR 0.61, 95% CI 0.4–0.94) were associated with improved OS. Pembrolizumab plus lenvatinib, nivolumab plus cabozantinib, pembrolizumab plus axitinib, and cabozantinib alone each showed improved PFS over sunitinib. Among these, pembrolizumab plus lenvatinib showed better PFS than pembrolizumab plus axitinib (HR 0.58, 95% CI 0.37–0.91), but no PFS difference compared to nivolumab plus cabozantinib (HR 0.63, 95% CI 0.39–1.03) and cabozantinib alone (HR 0.84, 95% CI 0.40–1.77). Network ranking showed pembrolizumab plus lenvatinib provided the favored OS and PFS benefit for elderly patients.

Conclusions

The combination of ICB with TKI such as pembrolizumab plus lenvatinib needs to be considered over monotherapy in the elderly population, but further validation using real-world data or prospective trials is necessary to confirm the efficacy and safety of first-line regimens for the geriatric population with advanced RCC.

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Data availability

Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information.

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Acknowledgements

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Funding

This research was not supported by a specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel. 281 1st Ave, New York, NY, 10003, USA

    Yu Fujiwara & Hirotaka Miyashita

  2. Division of Hematology and Oncology, Department of Medicine, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center. One Medical Center Drive, Lebanon, NH, 03766, USA

    Hirotaka Miyashita

  3. Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 325 West 15th Street, New York, NY, 10011, USA

    Bobby C. Liaw

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  1. Yu Fujiwara
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Contributions

YF helped in conceptualization, formal analysis, investigation, data curation, resources, statistical analysis, writing—original draft, and visualization. HM contributed to formal analysis, investigation, data curation, statistical analysis, writing—review & editing. BCL performed conceptualization, writing—review & editing, visualization, and supervision.

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Correspondence to Yu Fujiwara.

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Fujiwara, Y., Miyashita, H. & Liaw, B.C. First-line therapy for elderly patients with advanced renal cell carcinoma in the immuno-oncology era: a network meta-analysis. Cancer Immunol Immunother 72, 1355–1364 (2023). https://doi.org/10.1007/s00262-022-03341-y

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