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

Micah Ostrowski

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

https://orcid.org/0009-0004-2096-6352
Yeonjung Jo

Cancer Biostatistics, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Georges Gebrael

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Chadi Hage Chehade

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

https://orcid.org/0009-0008-6735-5777
Zeynep Irem Ozay

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

https://orcid.org/0000-0002-4827-9042
Blake Nordblad

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Ayana Srivastava

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Diya Garg

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Richard Ji

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Gliceida Galarza Fortuna

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Vinay Mathew Thomas

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Beverly Chigarira

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Ethan Anderson

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Neeraj Agarwal

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Benjamin Maughan

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Umang Swami

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA


Keywords

Immune Checkpoint Inhibitors; Metastasis; Renal Cell Carcinoma; Survival outcomes; Targeted therapy

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.

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