Therapies in Refractory Metastatic Renal Cell Carcinoma
As the therapeutic landscape for metastatic clear cell renal cell carcinoma (mccRCC) expands to include vascular
endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and immunotherapies, new challenges
are in place for evaluating and treating refractory disease. Assessing and managing refractory disease has several
elements: (1) the mechanism(s) of front-line treatment, (2) timing of progressive disease, (3) rapidity and sites of
progressing disease, (4) use of adjuvant therapy, and (5) incorporation of surgical and radiation techniques. These
variables all have distinct impact on the biology of refractory or resistant mccRCC. A better understanding of
the essential mechanisms of both primary and secondary immunotherapy resistance will inform biomarker
development and therapeutic strategies in the refractory setting. This paper addresses the current understanding
of treatment sequencing in refractory mccRCC, focusing on treatment options with prospective clinical trial data,
considers refractory mccRCC after adjuvant immunotherapy, and incorporates radiation or surgical resection for
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