Journal
THERAPEUTIC ADVANCES IN UROLOGY
Volume 8, Issue 5, Pages 319-326Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1756287216656811
Keywords
immunotherapy; nivolumab; programmed death-1; renal cell carcinoma
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Funding
- Bayer
- Bristol-Myers Squibb (BMS)
- Janssen
- Novartis
- Astellas
- Pfizer
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Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-a and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-alpha). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naive mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future.
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