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

• Published in: Cancer Immunology, Immunotherapy : CII Vol. 73; no. 9; p. 172
• Main Authors: Wu, Julie Tsu-Yu, Corrigan, June, Su, Chloe, Dumontier, Clark, La, Jennifer, Khan, Aparjita, Arya, Shipra, Harris, Alex H. S., Backhus, Leah, Das, Millie, Do, Nhan V., Brophy, Mary T., Han, Summer S., Kelley, Michael, Fillmore, Nathanael R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 02.07.2024; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - therapy; Chemotherapy; Female; Frailty; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunology; Immunotherapy; Immunotherapy - methods; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Non-small cell lung carcinoma; Oncology; Precision medicine; Small cell lung carcinoma; Frailty; Lung cancer; Performance status
• ISSN: 1432-0851; 0340-7004; 1432-0851
• DOI: 10.1007/s00262-024-03763-w

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.