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Treatment Decisions for Metastatic Clear Cell Renal Cell Carcinoma in Older Patients: The Role of TKIs and Immune Checkpoint Inhibitors

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Abstract

Given the underrepresentation of older patients in registration trials for metastatic renal cell carcinoma (mRCC), data to support the use of any particular systemic therapy over others, based on age, is limited. This is further complicated by clinical trials not commonly reporting adverse events by age. Thus, recommendations on treatment of older patients with mRCC are generally extrapolated from data on younger patients enrolled in these trials, which may not be ideal as many older patients are frail, have age-related organ dysfunction, or have multiple medical co-morbidities. In the last decade, the treatment landscape for mRCC has drastically changed with the approval of more than ten targeted therapies, as well as immune checkpoint inhibitors. Thus, treatment selection and sequencing of treatments can be especially challenging for clinicians. We begin this review by analyzing the available efficacy and toxicity data of these treatments in younger and older patients. We also discuss a network meta-analysis that compares the efficacy of these agents in older patients with mRCC. Utilizing this data, we suggest that nivolumab plus ipilimumab and cabozantinib may be favored for first-line treatment of specific populations of older patients. For salvage treatment, we suggest that cabozantinib may be the preferred agent for older patients.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    John Esther, Peter Hale & Andrew W. Hahn

  2. Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr, Suite 2161, Salt Lake City, UT, 84112, USA

    Neeraj Agarwal & Benjamin L. Maughan

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  1. John Esther
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  2. Peter Hale
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Corresponding authors

Correspondence to Neeraj Agarwal or Benjamin L. Maughan.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

John Esther, Peter Hale, and Andrew W. Hahn declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Neeraj Agarwal reports consultancy to the following: Pfizer, Novartis, Merck, Genentech, Eisai, Exelixis, Clovis, EMD Serono, BMS, Astra Zeneca, Foundation One, Astellas, Ely Lilly, Bayer, Argos, Medivation, Clovis, and Nektar. Neeraj Agarwal also reports research funding to his institution on his behalf from the following companies: Active Biotech, Astra Zeneca, Bavarian Nordic, BMS, Calithera, Celldex, Eisai, Exelixis, Genetech, GSK (glaxosmithkline), Immunomedics, Janssen, Medivation, Merck, New link Genetics, Novartis, Pfizer, Prometheus, Rexahn, Sanofi, Takeda, and Tracon. Benjamin L. Maughan reports consultancy to the following companies: Tempus, Exelixis, Peloton, and Janssen Oncology.

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Esther, J., Hale, P., Hahn, A.W. et al. Treatment Decisions for Metastatic Clear Cell Renal Cell Carcinoma in Older Patients: The Role of TKIs and Immune Checkpoint Inhibitors. Drugs Aging 36, 395–401 (2019). https://doi.org/10.1007/s40266-019-00644-1

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  • DOI: https://doi.org/10.1007/s40266-019-00644-1

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