The efficacy of second-line nivolumab versus tyrosine kinase inhibitors for renal cell carcinoma with bone metastases: A multi-institutional retrospective study

Immune checkpoint inhibitor combination therapy has been standardized for first-line treatment for metastatic renal cell carcinoma (mRCC), leading to the changes in second-line treatment options such as nivolumab or tyrosine kinase inhibitors (TKIs). However, there have been few reports comparing the efficacy of these drugs in mRCC patients, especially with bone metastases (BM), which are associated with a poor prognosis. Therefore, we aimed to compare the efficacy of nivolumab and TKIs as second-line treatments for 87 mRCC patients with BM and the microenvironments of the primary tumor and BM lesions. Multivariate analysis revealed poor risk according to the IMDC classification (p < 0.01) and high serum ALP value (p = 0.031) as worse prognostic factors, while there was no significant difference of overall survival between patients with nivolumab and TKIs. However, the objective response rate at BM lesions was significantly higher with TKIs than with nivolumab (p = 0.014). Immunohistochemistry analysis also revealed that VEGFR2 expression was significantly higher at BM lesions compared to that in primary tumors, showing the potential benefit of TKIs over nivolumab in mRCC patients with BM. In conclusion, TKIs could be the promising second-line treatment for mRCC with metastasis limited to the bone.