Nathanael R. Fillmore
Publications / 2024
paper
Cancer Immunology, Immunotherapy2024doi:10.1007/s00262-024-03763-w

The performance status gap in immunotherapy for frail patients with advanced non-small cell lung cancer.

Julie Tsu-Yu Wu, June Corrigan, Chloe Su, Clark Dumontier, Jennifer La, Aparjita Khan, Shipra Arya, Alex H. S. Harris, Leah Backhus, Millie Das, Nhan V. Do, Mary T. Brophy, Summer S. Han, Michael Kelley, Nathanael R. Fillmore

Summary

Patients with frailty are less likely to receive intensive immunotherapy combinations for advanced non-small cell lung cancer regardless of their overall performance status. However, performance status remains the primary driver of survival for those receiving intensive treatment, as frailty does not significantly impact outcomes in patients who already have a poor performance status.

Key result

Frail patients with good performance status receiving intensive treatment had significantly lower overall survival compared to non-frail patients (hazard ratio 1.53, 95% CI 1.2-1.96), whereas no such association existed for those with poor performance status (hazard ratio 1.03, 95% CI 0.67-1.58).

Abstract

PURPOSE: In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown. METHODS: Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy. RESULTS: Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58). CONCLUSION: Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.

Key figure

Key figure from The performance status gap in immunotherapy for frail patients with advanced non-small cell lung cancer.