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) 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.