An Illustrative Case of Combination Cabozantinib/Nivolumab for Progressive Metastatic Renal Cell Carcinoma (mRCC).

We report a case using combination cabozantinib/nivolumab to salvage disease control in a patient with refractory metastatic renal cell carcinoma (mRCC). The patient had previously experienced disease progression from high dose IL-2, sunitinib, pazopanib, cabozantinib, and nivolumab, all given sequentially. Combination cabozantinib/nivolumab resulted in 22 months of disease control. Vascular endothelial growth factor (VEGF) inhibitors including cabozantinib have immunomodulatory effects when combined with immune checkpoint inhibitors, with multiple ongoing phase 3 trials exploring the cabozantinib/nivolumab combination in the first line setting. To our knowledge, this is the first reported case of progression on nivolumab and cabozantinib when given as sequential monotherapies but stable disease on combination cabozantinib/nivolumab. IMPLICATIONS FOR PRACTICE: There is ongoing evaluation of combination VEGF-targeted therapies and immune checkpoint inhibitors given their potential mechanistic synergy. With the recent CHECKMATE 9ER press release reporting clinically meaningful benefit from the combination cabozantinib/nivolumab compared to sunitinib in the first line setting, this case of sustained stable disease with combination cabozantinib/nivolumab after progression on prior VEGF-targeting therapies and immunotherapies highlights the activity of this combination as a potential treatment alternative to improve disease control.

The oncologist. 2020 Nov 29 [Epub ahead of print]

Chester Kao, Daniel J George, Tian Zhang

Division of Medical Oncology, Department of Medicine, Durham, NC, 27710.