Background: Immune checkpoint inhibitors targeting the programmed death receptor lig-and 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represent a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients. Objective: In this review, we focused on trials that investigated the administration of a PD-1 and PD-L1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as a prognostic and predictive biomarker. Conclusion: So far, the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of antibiotic therapy. Combinations of different biomarkers and biological features, such as gene expression associated with angiogenesis, immune response and mye-loid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.
Cimadamore A., Massari F., Santoni M., Lopez-Beltran A., Cheng L., Scarpelli M., et al. (2020). PD1 and PD-L1 inhibitors for the treatment of kidney cancer: The role of PD-L1 assay. CURRENT DRUG TARGETS, 21(16), 1664-1671 [10.2174/1389450121666200324151056].
PD1 and PD-L1 inhibitors for the treatment of kidney cancer: The role of PD-L1 assay
Massari F.;
2020
Abstract
Background: Immune checkpoint inhibitors targeting the programmed death receptor lig-and 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represent a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients. Objective: In this review, we focused on trials that investigated the administration of a PD-1 and PD-L1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as a prognostic and predictive biomarker. Conclusion: So far, the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of antibiotic therapy. Combinations of different biomarkers and biological features, such as gene expression associated with angiogenesis, immune response and mye-loid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
