Promising predictors of checkpoint inhibitor response in NSCLC

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.