Recent advances in the systemic treatment of metastatic non-clear cell renal cell carcinomas

Abstract

There is still no standard treatment for non-clear cell renal cell carcinomas. Sunitinib is the most examined drug because of its effectiveness in retrospective studies and clinical trials, and is the preferred first-line drug in the National Comprehensive Cancer Network guideline. Temsirolimus is an option as a first-line drug, especially for poor-risk non-clear cell renal cell carcinoma patients. Everolimus, pazopanib, axitinib and nivolmab might also be viable options. Clinical trials are still required to gather evidence regarding non-clear cell renal cell carcinoma treatment. Because each non-clear cell renal cell carcinoma has a different genetic background and molecular features, specific treatment for each non-clear cell renal cell carcinoma should be established. From the results of a Japanese multicenter study, tyrosine kinase inhibitors might be better used for metastatic papillary renal cell carcinoma in both first- and second-line settings. Both tyrosine kinase inhibitors and mammalian target of rapamicin inhibitors are effective for metastatic chromophobe renal cell carcinoma, but the preferred first-line drug has not been determined. Platinum-based chemotherapies are currently recommended for metastatic collecting duct carcinoma, and anti-angiogenic drugs are effective in some cases. Tyrosine kinase inhibitors, especially sunitinib, appear to be effective for X11.2 translocation renal cell carcinoma among the microphthalmia-associated transcription family of translocation renal cell carcinomas. Evidence is still lacking regarding the treatment for other rare non-clear cell renal cell carcinomas. Appropriate sequential therapies using antivascular endothelial growth factor therapies, mammalian target of rapamicin inhibitors and immuno-oncology drugs should be established for each non-clear cell renal cell carcinoma.

Keywords: immuno-oncology drug; mammalian target of rapamicin inihibitor; non-clear cell renal cell carcinoma; targeted therapy; tyrosine kinase inhibitor.