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Review
. 2021 Dec 24;12(1):24.
doi: 10.3390/life12010024.

Immunotherapy and Metastatic Renal Cell Carcinoma: A Review of New Treatment Approaches

Nikhita Kathuria-Prakash  1   2 , Claire Drolen  1 , Christopher A Hannigan  1   2 , Alexandra Drakaki  1   2
Affiliations
Review

Immunotherapy and Metastatic Renal Cell Carcinoma: A Review of New Treatment Approaches

Nikhita Kathuria-Prakash et al. Life (Basel). .

Abstract

Introduction: Renal cell carcinomas (RCC) have been treated with immunotherapy for decades; the use of immune checkpoint inhibitors represents the most recent advance. In this review, we compare these new RCC immunotherapies, with a focus on achieving durable complete responses (CR).

Review: Sorafenib and sunitinib were the first Food and Drug Administration (FDA)-approved targeted agents for RCC, with sunitinib eventually becoming the standard-of-care agent against which novel therapies are compared. In the last five years, many combination therapies based on the use of immune checkpoint inhibitors (ICIs) and receptor tyrosine kinase inhibitors (TKIs), including ipilimumab/nivolumab, nivolumab/cabozantinib, avelumab/axitinib, pembrolizumab/axitinib, and pembrolizumab/lenvatinib, have demonstrated superior overall survival (OS) and progression-free survival (PFS) compared to sunitinib. Ongoing clinical trials of hypoxia-induced factor-2 alpha (HIF-2a) inhibitors, chimeric antigen receptor T cell (CAR-T) therapy targeting CD70, and other new combination therapies have also shown promise and are currently under investigation.

Conclusions: Many new combination therapies are approved for RCC treatment, and CR rates suggest that, in the era of immunotherapy, it may be possible to achieve durable responses and survival benefit in patients with metastatic RCC.

Keywords: complete response rate; immune checkpoint inhibitors; immunotherapy; renal cell carcinoma; sunitinib.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Directions for future RCC therapies [41,42,43,45,46,47,48].
Figure 2
Figure 2
Mechanisms of future RCC therapies.
See this image and copyright information in PMC

References

    1. Cancer of the Kidney and Renal Pelvis—Cancer Stat Facts SEER. [(accessed on 30 August 2021)]; Available online: https://seer.cancer.gov/statfacts/html/kidrp.html.
    1. Negrier S., Escudier B., Lasset C., Douillard J.-Y., Savary J., Chevreau C., Ravaud A., Mercatello A., Peny J., Mousseau M., et al. Recombinant Human Interleukin-2, Recombinant Human Interferon Alfa-2a, or Both in Metastatic Renal-Cell Carcinoma. N. Engl. J. Med. 1998;338:1272–1278. doi: 10.1056/NEJM199804303381805. - DOI - PubMed
    1. Fyfe G., Fisher R.I., Rosenberg S.A., Sznol M., Parkinson D.R., Louie A.C. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J. Clin. Oncol. 1995;13:688–696. doi: 10.1200/JCO.1995.13.3.688. - DOI - PubMed
    1. McDermott D.F., Regan M.M., Clark J.I., Flaherty L.E., Weiss G.R., Logan T.F., Kirkwood J.M., Gordon M.S., Sosman J.A., Ernstoff M.S., et al. Randomized Phase III Trial of High-Dose Interleukin-2 Versus Subcutaneous Interleukin-2 and Interferon in Patients with Metastatic Renal Cell Carcinoma. J. Clin. Oncol. 2005;23:133–141. doi: 10.1200/JCO.2005.03.206. - DOI - PubMed
    1. McDermott D.F., Cheng S.-C., Signoretti S., Margolin K., Clark J.I., Sosman J.A., Dutcher J.P., Logan T.F., Curti B.D., Ernstoff M.S., et al. The High-Dose Aldesleukin “Select” Trial: A Trial to Prospectively Validate Predictive Models of Response to Treatment in Patients with Metastatic Renal Cell Carcinoma. Clin. Cancer Res. 2015;21:561–568. doi: 10.1158/1078-0432.CCR-14-1520. - DOI - PMC - PubMed