# First-Line Ipilimumab with Nivolumab versus Immune Checkpoint Inhibitors with Tyrosine Kinase Inhibitors in Patients with Intermediate- or Poor-Risk Metastatic Clear Cell Renal Cell Carcinoma

## TL;DR

This study compares two first-line treatments for advanced kidney cancer and finds similar survival but faster disease progression with one option.

## Contribution

Provides real-world evidence comparing Ipi + Nivo and ICI + TKI for mccRCC without prior head-to-head trials.

## Key findings

- Real-world overall survival was comparable between Ipi + Nivo and ICI + TKI.
- Ipi + Nivo had significantly shorter time to next therapy compared to ICI + TKI.
- Findings offer clinical guidance for selecting first-line treatment in mccRCC.

## Abstract

Ipilimumab with nivolumab (Ipi + Nivo) and immune checkpoint inhibitors with tyrosine kinase inhibitors (ICI + TKI) are the first-line approved treatments for intermediate- and poor-risk metastatic clear cell renal cell carcinoma (mccRCC); however, they have not been compared head-to-head in prospective trials to guide treatment selection. Thereupon, we sought to compare survival outcomes of patients receiving first-line Ipi + Nivo versus ICI + TKI, using a large, real-world database among patients with intermediate- and poor-risk mccRCC. This retrospective cohort study used a nationwide electronic health record-derived deidentified database, where patients with mccRCC with intermediate- or poor-risk who received first-line Ipi + Nivo or ICI + TKI between 20 June, 2016, and 26 January, 2023, were included. Primary outcomes were real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS), summarized via Kaplan-Meier survival estimates with 95% confidence intervals (CIs) and compared in the context of propensity score (PS) matching weighted analysis. Of the 12,707 patients in the dataset, 1,438 with mccRCC met eligibility and were included. After PS matching weighted analysis, no significant difference in rwOS was noted between both groups (HR 1.01, 95% CI 0.86–1.19; p = 0.91); however, rwTTNT was significantly shorter with Ipi + Nivo than with ICI + TKI (HR 0.78, 95% CI 0.68–0.89; p < 0.001). In this large real-world study, there was evidence that rwOS was comparable, while rwTTNT was superior in patients receiving ICI + TKI compared to those receiving Ipi + Nivo. These real-world data offer important guidance for clinicians in choosing between Ipi + Nivo and ICI + TKI as frontline treatment.