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

Abstract

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. The Oncologist 2020;9999:• • 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.

TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells

“…Recently, results of a clinical trial (the COSMIC-021 trial) mentioned that Cabozantinib (an anti-angiogenesis drug that also targets MET) could be benefit for treatment (44). Therefore, it is valuable to focus on the significance of c-MET and the small molecular inhibitor of c-MET in the PC treatment (45,46).…”

Exploring the synergistic effects of cabozantinib and a programmed cell death protein 1 inhibitor in metastatic renal cell carcinoma with machine learning

“…Nonclinical [ 72 , 73 ] and clinical studies [ 74 ] point to a synergistic antitumor activity of cabozantinib combined with a PD1 inhibitor in patients with mRCC [ 11 , 14 ], but just a few have delved into the biological basis of the effect. Primary and metastatic prostate mouse tumour models revealed synergistic efficacy when combining cabozantinib with a dual checkpoint inhibitor therapy (CPI, anti-PD1/anti-CTLA-4) that inactivated MDSCs suppressive activity on cytotoxic T-cell proliferation.…”