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

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 (P_ref), exhibit progressive disease as their best response and have poor outcomes.

Purpose of the Study:

• To determine the prevalence and clinicopathological characteristics of P_ref 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 (P_ref) rate was 19%.
• Nivolumab/ipilimumab had the highest P_ref rate (27%), while pembrolizumab/lenvatinib had the lowest (10%).
• P_ref patients had significantly shorter median overall survival (7.6 months) versus non-P_ref patients (55.7 months).
• Predictors for overall survival in P_ref 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 P_ref.

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 P_ref patients.