Related Experiment Video

Updated: Jun 12, 2025

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

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Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma

Daniele Santini1, Haoran Li2, Giandomenico Roviello3

  • 1Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I, University of Rome, Rome, Italy.

Targeted Oncology
|September 17, 2024
PubMed
Abstract

Insights

In renal cell carcinoma, 19% of patients receiving first-line immunotherapy combinations are primary refractory (Pref), facing significantly worse survival. Predictors like liver metastases and poor risk indicate higher Pref risk.

Area of Science:

  • Oncology
  • Immunotherapy
  • Renal Cell Carcinoma Research

Background:

  • Immuno-oncology combinations have transformed renal cell carcinoma (RCC) treatment.
  • However, a subgroup of patients, termed primary refractory (Pref), exhibit progressive disease as their best response and have poor outcomes.

Purpose of the Study:

  • To determine the prevalence and clinicopathological characteristics of Pref patients with metastatic clear cell RCC.
  • To identify predictors of primary refractoriness and overall survival in this patient subgroup.

Main Methods:

  • Multicenter retrospective real-world study involving 1709 patients from 72 centers across 22 countries.
  • Patients received first-line immune-oncology combinations for metastatic clear cell RCC.
  • Statistical analyses included Kaplan-Meier, Cox proportional hazard models, logistic regression, and ROC curve analysis.

Main Results:

  • The overall primary refractory (Pref) rate was 19%.
  • Nivolumab/ipilimumab had the highest Pref rate (27%), while pembrolizumab/lenvatinib had the lowest (10%).
  • Pref patients had significantly shorter median overall survival (7.6 months) versus non-Pref patients (55.7 months).
  • Predictors for overall survival in Pref patients included nephrectomy, sarcomatoid de-differentiation, poor risk status, and bone/brain metastases.
  • Liver metastases, poor risk status, and no surgery were associated with an increased risk of Pref.

Conclusions:

  • The study highlights the challenges associated with the primary refractory subgroup in RCC.
  • Identified predictors can aid in risk stratification for tailored therapeutic strategies in Pref patients.

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