Intrapatient Tumor Heterogeneity in IHC Interpretation Using PD-L1 IHC 22C3 pharmDx.

Tumor heterogeneity may impact immunohistochemical (IHC) interpretation, thus potentially affecting decision making by treating oncologists for cancer patient management. Programmed cell death ligand-1 (PD-L1) IHC 22C3 pharmDx is a companion diagnostic used as an aid in identifying patient eligibility for treatment with pembrolizumab (KEYTRUDA). This study aims to investigate tumor heterogeneity impact on IHC staining when evaluating PD-L1 expression using PD-L1 IHC 22C3 pharmDx. The effect of tumor heterogeneity was evaluated based on the PD-L1 diagnostic status of PD-L1 IHC 22C3 pharmDx stained tumor tissue sections at relevant diagnostic cutoffs for non-small cell lung carcinoma, gastric or gastroesophageal junction adenocarcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, esophageal cancer and triple negative breast cancer. Overall agreement for the PD-L1 diagnostic status was assessed for each tumor type within a given specimen block (Intra-Block), between specimen blocks from the same surgical resection (Intra-Case), and between intrapatient primary and metastatic specimens. Intrablock and intracase point estimates were above 75%, and primary versus metastatic point estimates were above 50%. The results suggest that PD-L1 expression is consistent across cut sections through a minimum of 150 µm within a tissue block and between blocks from the same surgical resection and is significantly maintained across primary and metastatic blocks from the same patient despite changes to the tissue microenvironment. These data provide confidence for histopathologists and oncologists that evaluation of PD-L1 expression at clinically relevant cutoffs is reproducible among different assessments (or samplings) of a single tumor specimen.