Midterm Outcomes of Combination Therapy With Immune Checkpoint Inhibitors and VEGFR ‐ TKIs in Real‐World Patients With Advanced Renal Cell Carcinoma

ABSTRACT Background Limited data are available on the midterm outcomes of combination therapy with immune checkpoint inhibitors and VEGFR‐TKIs (IO‐TKI) for advanced renal cell carcinoma (RCC) in real‐world settings. Methods We retrospectively evaluated 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 initiated IO‐TKI at least 3 years before the data‐cutoff, ensuring a potentially minimum follow‐up of 3 years. 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. 13.8 months, p = 0.0503) and OS (not reached vs. 37.4 months, p = 0.0016) 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 glucocorticoids (≥ 40 mg prednisone/day) were required in 10 patients (15%). Conclusion With a minimum of 3 years of follow‐up, IO‐TKI demonstrated feasible effectiveness and manageable safety in patients with advanced RCC in the real world. More effective treatment strategies and novel therapeutic targets are needed for patients with non‐clear‐cell RCC.