Midterm outcomes of combination therapy with immune checkpoint inhibitors and VEGFR-TKIs in real-world patients with advanced renal cell carcinoma

Background Limited data are available on the midterm outcomes of combination therapy with immune checkpoint inhibitors and VEGFR-TKIs (IO-TKI therapy) for advanced renal cell carcinoma (RCC) in real-world settings. Methods We retrospectively evaluated clinical data from 68 patients who received lenvatinib plus pembrolizumab (n = 14), cabozantinib plus nivolumab (n = 20), pembrolizumab plus axitinib (n = 23), or avelumab plus axitinib (n = 11) as first-line therapy for advanced RCC. All patients had a minimum follow-up of 3 years after treatment initiation. Effectiveness and safety profiles were assessed. Results During a median follow-up of 32.7 months, the median progression-free survival (PFS) and overall survival (OS) were 19.9 and 46.7 months, respectively. The objective response rate was 57%. In subgroup analysis, histology was associated with survival outcomes; median PFS (23.0 vs. 8.97 months, p = 0.0362) and OS (not reached vs. 32.1 months, p = 0.0005) were longer in patients with clear-cell RCC than in those with non-clear cell RCC. Regarding safety, grade ≥ 3 adverse events occurred in 44 patients (65%). Treatment discontinuation of both drugs was required in 14 patients (21%), and discontinuation of one drug in 21 patients (31%). High-dose corticosteroids (≥ 40 mg prednisone/day) were required in 10 patients (15%). Conclusion With a minimum of 3 years of follow-up, IO-TKI therapy demonstrated feasible effectiveness and manageable safety in patients with advanced RCC in real-world. More effective treatment strategies and novel therapeutic targets are needed for patients with non-clear cell RCC.