Predictive biomarkers for programmed death-1/programmed death ligand immune checkpoint inhibitors in nonsmall cell lung cancer

Immune checkpoint inhibitors, antiprogrammed death receptor 1 (anti-PD-1)/antiprogrammed death-ligand 1 (anti-PD-L1), are new therapeutic regimens for managing advanced nonsmall cell lung cancer patients, giving an overall response rate of approximately 20% as monotherapy in second-line treatment. The use of predictive biomarkers for identifying patients suitable for these therapies is an important issue not only for making treatment decisions, but also from a medical economic point of view.Among potential predictive biomarker candidates for anti-PD-1/PD-L1 treatments in nonsmall cell lung cancer, the expression of PD-L1 (as determined by immunohistochemistry) is currently the most studied. PD-L1 positivity has been associated with higher response rate to anti-PD-1/PD-L1 therapies. However, several observations suggest that the predictive value of PD-L1 expression is not clear-cut. We review other potential predictive biomarkers, including programmed death-ligand 2, IFN-γ, and genetic signatures.Standardized techniques and conditions for evaluating PD-L1 expression (tissue quality and age, percentage positivity threshold, managing heterogeneous and dynamic expression) are critical for establishing the use of this protein as a predictive marker. Care should be also taken when using anti-PD-1/PD-L1 therapies in combination with other therapies, which may impact the predictive value of PD-L1 expression.