“For patients who have intermediate or poor risk disease, I think nivolumab plus ipilimumab should be considered the new standard of care,” Dr McGregor said.

Among the 249 patients CheckMate-214 with favorable risk, however, sunitinib was superior to the immunotherapy combination in terms of objective response rate (52% vs 29%, respectively) and median PFS (25.1 months vs 15.3 months). “With the data we have right now, I would feel more comfortable starting a patient with favorable risk with a TKI (such as sunitinib) and then using immunotherapy as a second line,” Dr McGregor said.

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First-Line Contenders

“Up until the recent CheckMate 214 data, nothing was better than sunitinib,” Dr McGregor said. Sunitinib is an inhibitor of multiple tyrosine kinase receptors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, which are important for angiogenesis.

The early efficacy data with sunitinib “spawned a variety of other TKIs,” Dr McGregor said. One of them is pazopanib, which, along with sunitinib, is the preferred first-line therapy for advanced RCC, according to National Comprehensive Cancer Network (NCCN) guidelines.6

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There are, however, a number of ongoing clinical trials evaluating various combinations of immunotherapies and TKIs in the first-line setting in patients with advanced or metastatic RCC. CheckMate-9ER will, for example, compare the efficacy of nivolumab and ipilimumab plus the TKI, cabozantinib, with either nivolumab plus cabozantinib or sunitinib alone.7 The CLEAR trial will compare lenvatinib in combination with pembrolizumab or the mTOR kinase inhibitor, everolimus, with sunitinib alone.8 CheckMate 016, a phase 1 trial, is comparing nivolumab in combination with sunitinib or pazopanib.9

“It will be intriguing, as we get data moving forward, if any of these will be superior to nivolumab and ipilimumab” based on cross trial analyses, Dr McGregor said.