Large-Scale Meta-Analysis of Potential Biomarkers for Treatment Response to Anti-PD-1/PD-L1 Immune Checkpoint Inhibitors
Mariam, A.; Kamath, S.; Schveder, K.; McLeod, H. L.; Rotroff, D. M.
Show abstract
Immune checkpoint inhibitors (ICIs) blocking programmed death receptor 1 or its ligand (anti-PD-1/PD-L1) are a burgeoning class of promising cancer treatments. However, not all patients respond to these treatments. Although studies have suggested potential biomarkers to predict patients likely to respond to treatment, no consensus biomarker has been identified. Here, 95 peer-reviewed studies representing 18,978 subjects across 15 cancer types were meta-analyzed to determine biomarkers that best predicted ICI response within and across cancers. Performance was assessed using the sensitivity, specificity, area under the receiver operating characteristic curve, and others. Across all cancers, multimodal biomarkers and tumor mutational burden discriminated ICI response better than PD-L1 immunohistochemistry assays (IHC) (P=.04) with sensitivities of 0.57 and 0.70 and specificities of 0.76 and 0.53, respectively. Marginal improvements were also observed for nascent microbiome biomarkers compared to IHC (P=.06). Current ICI biomarker performances indicate that additional research is needed to develop highly accurate and precise biomarkers for widespread clinical adoption.
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