Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma.

To retrospectively evaluate the differential efficacy of immuno-oncology (IO)-IO and IO-tyrosine kinase inhibitor (TKI) combination therapies based on metastatic site in patients with metastatic renal cell carcinoma. Methods: This retrospective analysis used data from a multicenter study conducted by the JK-FOOT Study Group. A total of 579 patients with mRCC who treated with first-line combination immunotherapy between September 2018 and December 2024 were included in the study. Patients with metastases in the lymph nodes, lung, bone, liver, brain, and other distant sites were analyzed for progression-free survival (PFS) and overall survival (OS) according to metastatic site. Only patients with intermediate- or poor-risk disease, as defined by the International Metastatic RCC Database Consortium (IMDC) risk group, were included. The primary outcomes were PFS and OS, and the secondary outcome was objective response rate (ORR), with a comparison between the IO-IO and IO-TKI groups. Results: In patients with lymph node metastases (n = 38), lung metastases (n = 141), and brain metastases (n = 18), there were no significant differences in overall survival (OS) or progression-free survival (PFS) between the IO-IO and IO-TKI groups. In patients with bone metastases (n = 85), there was a trend toward improved OS in the IO-TKI group compared to the IO-IO group (P = 0.053), while in patients with liver metastases (n = 24), OS was significantly longer in the IO-TKI group (P = 0.011). Conclusions: For patients with metastatic renal cell carcinoma and bone or liver metastases, IO-TKI combination therapy is a more appropriate treatment option than IO-IO therapy.