Abstract
Significant progress has been made in the management of renal cell carcinoma (RCC) during the last few decades. In early stage, localized disease, surgical resection remains the modality of choice, with no therapeutic interventions as options for post-operative therapy other than simple observation and clinical surveillance. However, treatment options in the advanced or metastatic setting are increasing at a dizzying pace, initially with cytokine therapy, then with the increased availability of targeted therapy including novel small-molecule inhibitors of receptor tyrosine kinases and monoclonal antibodies targeting novel proteins, establishing them as the current standard of care. Even more recently, immunotherapy has seen tremendous development in the form of immune checkpoint inhibition and vaccines. Overall, these interventions have gradually changed the landscape of cancer management in general, and metastatic renal cell carcinoma (mRCC) in particular. This is exemplified by the recent United States Food and Drug Administration (USFDA) approval of nivolumab for patients with mRCC after failure of TKI therapy. In this review, we present a brief overview of the current management of mRCC, primarily the clear cell subtype (ccRCC), and discuss the major clinical trials and data on the immunotherapy in advanced or mRCC.
Highlights
Therapeutic modalities for cancer management have primarily consisted of surgery, radiotherapy and chemotherapy
We present a brief overview of the current management of metastatic renal cell carcinoma (mRCC), primarily the clear cell subtype, and discuss the major clinical trials and data on the immunotherapy in advanced or mRCC
Cytokine therapy involving IL-2 and IFN-α was the mainstay of mRCC treatment
Summary
Therapeutic modalities for cancer management have primarily consisted of surgery, radiotherapy and chemotherapy. Temsirolimus was found www.impactjournals.com/oncotarget to have improved PFS and OS compared to IFN-α, while the combination did not yield additional benefit despite an increase in adverse events [21] Based on these data, temsirolimus is approved for first-line treatment of “poor” risk metastatic RCC. Nivolumab (Opdivo®, Bristol-Myers Squibb, Princeton, NJ) is a fully human IgG4 anti-PD-1 immune checkpoint inhibitor monoclonal antibody It has been studied extensively in various cancers, and has received approval by the USFDA for the treatment of mRCC, in addition to metastatic melanoma and squamous and nonsquamous non-small cell lung cancer, and more recently, in Hodgkin Disease [68, 69]. Various randomized trials of adjuvant therapy involving tumor cells plus BCG, tumor cell vaccination, IFN-α, high-dose IL-2, or a combination of cytokines have not demonstrated survival benefit when compared with observation [114]. There is an ongoing clinical trial evaluating radiation therapy in combination with pembrolizumab for patients with recurrent or mRCC [NCT02318771] [117]
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