Comparative Analysis of Immune-based Combination Therapy as First-line Treatment for Advanced Renal Cell Carcinoma

In advanced renal cell carcinoma (RCC), immune checkpoint inhibitor (ICI) combinations (ICI-ICI) and ICI plus tyrosine kinase inhibitor (TKI) combinations (ICI-TKI) are standard first-line therapies. However, real-world data directly comparing these approaches remain limited. This study aimed to compare treatment outcomes between ICI-ICI and ICI-TKI therapies.

We retrospectively analyzed 58 patients who received first-line ICI-ICI therapy (ipilimumab plus nivolumab) or ICI-TKI therapy (pembrolizumab plus axitinib, avelumab plus axitinib, nivolumab plus cabozantinib, or pembrolizumab plus lenvatinib) for advanced RCC at Nagasaki University Hospital (March 2018 to June 2024). Primary endpoints were progression-free survival (PFS), overall survival, and objective response rate (ORR). Safety profiles were also evaluated.

We included 36 patients in the ICI-ICI group and 22 in the ICI-TKI group. The median follow-up was 17.5 months. The median age of patients in the ICI-TKI group was significantly older than that in the ICI-ICI group (74 vs. 66 years, p<0.001). The median PFS was 30 months in the ICI-ICI group and 25 months in the ICI-TKI group. The median overall survival was 51 months in the ICI-ICI group and 49 months in the ICI-TKI group, with no significant difference observed for either endpoint. The ORR was also similar between the groups. Notably, two complete responses occurred in the ICI-ICI group. The treatment discontinuation rate due to grade ≥3 adverse events was not significantly different between the ICI-ICI and ICI-TKI groups (30.6% vs. 40.9%).

Across all International Metastatic RCC Database Consortium risk groups, PFS, OS, and ORR showed no significant differences between ICI-ICI and ICI-TKI therapies. Treatment selection should consider patient-specific factors. Validation through larger prospective studies is warranted.