Combinations of immuno-checkpoint inhibitors predictive biomarkers only marginally improve their individual accuracy

There are no accepted universal biomarkers capable to accurately predict response to immuno-checkpoint inhibitors (ICI). Although recent literature has been flooded with studies on ICI predictive biomarkers, available data show that currently approved companion diagnostics either leave out many possible responders, as in the case of PD-L1 testing for first-line metastatic lung cancer, or apply to a small subset of patients, such as the recently approved treatment for microsatellite instability-high or mismatch repair deficiency tumors. In this study, we conducted a survey of the available data on ICI trials with matched genomic or transcriptomic datasets in order to cross-validate the proposed biomarkers, to assess whether their prediction power was confirmed and, mainly, to investigate if their combination was able to generate a better predictive tool.