Promising predictors of checkpoint inhibitor response in NSCLC
Friedlaender Alex1, Addeo Alfredo1
1Department of Oncology, University Hospital Geneva , Geneva, Switzerland.
Introduction:
The development of immune-checkpoint inhibitors targeting the programmed death-1 (PD-1) and its ligand (PD-L1) axis has transformed the treatment paradigm in non-small-cell lung cancer, bringing about unprecedented 5-year survival rates. Despite this dramatic improvement, roughly 70% of patients do not derive durable benefit from these treatments, illustrating the need for predictive biomarkers.
Areas Covered:
In this review, we will discuss what makes a successful biomarker and analyze the role and significance of currently available options, including PD-L1, oncogenic alterations and tumor mutation burden. We then discuss potential biomarkers on the horizon, including the microbiome, tumor infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, gene signatures and the emerging field of multiomics.
Expert Opinion:
To date, only PD-L1 is clinically validated as a positive predictor of response to immunotherapy, yet the need to refine patient selection has never been stronger, given the indication for checkpoint inhibitors alone or in combination in all non-oncogene driven non-small-cell lung cancer patients receiving front-line therapy. Prospective validation of the above-mentioned potential biomarkers, either alone or in combination, may help to elaborate improved predictive tools.
Insights
Predictive biomarkers are crucial for improving immunotherapy response in non-small-cell lung cancer. This review analyzes current biomarkers like programmed death-1 (PD-1) and explores emerging options to enhance patient selection for better outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immune-checkpoint inhibitors targeting the programmed death-1 (PD-1) and programmed death-1 ligand (PD-L1) axis have revolutionized non-small-cell lung cancer (NSCLC) treatment.
- Despite advancements, approximately 70% of patients lack durable benefit, highlighting the critical need for predictive biomarkers.
Purpose of the Study:
- To review the characteristics of successful biomarkers for immunotherapy response in NSCLC.
- To analyze the utility of current biomarkers (PD-L1, oncogenic alterations, tumor mutation burden).
- To discuss emerging biomarkers such as microbiome, tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, gene signatures, and multi-omics.
Main Methods:
- Literature review and analysis of existing and potential predictive biomarkers for immunotherapy in NSCLC.
- Discussion of the clinical validation and future prospects of various biomarkers.
Main Results:
- Programmed death-1 ligand (PD-L1) is currently the only clinically validated positive predictor of response to immunotherapy.
- Several novel biomarkers show promise for refining patient selection, including microbiome, tumor-infiltrating lymphocytes, and multi-omics approaches.
Conclusions:
- Refining patient selection for immune-checkpoint inhibitors in NSCLC is essential, especially with expanding indications for front-line therapy.
- Prospective validation of emerging biomarkers, individually or in combination, is necessary to develop improved predictive tools for immunotherapy response.
