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Predictive Biomarkers for Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: Current Status and
Sheena Bhalla1, Deborah Blythe Doroshow, Fred R Hirsch
1From the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Abstract:
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for advanced non-small cell lung cancer (NSCLC). Although certain patients achieve significant, long-lasting responses from checkpoint blockade, the majority of patients with NSCLC do not and may be unnecessarily exposed to inadequate therapies and immune-related toxicities. Therefore, there is a critical need to identify biomarkers predictive of immunotherapy response. While tumor and immune cell expression of programmed death ligand-1 and, more recently, tumor mutational burden are used in clinical practice and may correlate with immunotherapy response in selected circumstances, neither consistently predicts an individual patient's likelihood of clinical benefit from ICI therapy. More recently, innovative approaches such as blood-based assays and combination biomarker strategies are under active investigation. This review will focus on the current role and challenges of programmed death ligand-1 and tumor mutational burden as predictive biomarkers for immunotherapy response in advanced NSCLC and explore promising novel biomarker strategies.
Insights
Identifying reliable biomarkers is crucial for predicting immunotherapy response in advanced non-small cell lung cancer (NSCLC). Current markers like programmed death ligand-1 and tumor mutational burden show limitations, necessitating novel strategies for better patient selection.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) have transformed advanced non-small cell lung cancer (NSCLC) treatment.
- However, many NSCLC patients do not respond to ICIs and face potential toxicities.
- Predictive biomarkers are essential to identify patients likely to benefit from immunotherapy.
Purpose of the Study:
- To review the current role and limitations of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) as predictive biomarkers for ICI therapy in advanced NSCLC.
- To explore emerging biomarker strategies for improving immunotherapy response prediction.
Main Methods:
- Literature review focusing on PD-L1 expression and TMB in NSCLC.
- Analysis of current clinical practices and challenges in biomarker utilization.
- Exploration of novel biomarker approaches, including blood-based assays and combination strategies.
Main Results:
- PD-L1 expression and TMB are currently used but lack consistent predictive power for individual NSCLC patients.
- Neither biomarker reliably predicts clinical benefit across the entire NSCLC patient population.
- Significant limitations exist in the current application of these biomarkers.
Conclusions:
- There is a critical need for more accurate predictive biomarkers in advanced NSCLC immunotherapy.
- Novel strategies, such as liquid biopsies and multi-marker panels, show promise for enhanced patient stratification.
- Further research into innovative biomarkers is vital for optimizing ICI therapy efficacy and minimizing patient exposure to ineffective treatments.
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