Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP)

Abstract

Since 2014, programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-approved, commercially available companion/ complementary diagnostic assays that were clinically validated using data from their corresponding clinical trials. The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immunooncology therapies targeting the PD-1/PD-L1 checkpoint. These recommendations are issued as 38 Guideline Statements that address (i) assay development for surgical pathology and cytopathology specimens, (ii) reporting elements, and (iii) quality assurance (including validation/verification, internal quality assurance, and external quality assurance). The intent of this work is to provide recommendations that are relevant to any tumor type, are universally applicable and can be implemented by any clinical immunohistochemistry laboratory performing predictive PD-L1 immunohistochemistry testing.

PD-L1 Testing and Squamous Cell Carcinoma of the Head and Neck: A Multicenter Study on the Diagnostic Reproducibility of Different Protocols

“…The Food and Drug Administration (FDA) approved the 22c3 clone on the Autostainer platform as CDx on the basis of the demonstration of an overall percent agreement ranging from 95.7% to 97.8% in evaluating CPS > 1 and 92.1% to 97.3% for CPS > 20 [ 13 ]. However, the large employment of different tools for the purpose stimulated the comparison of diagnostic performances among different protocols, leading the College of American Pathologists to suggest a minimum sensitivity and specificity of 90% independently from the employed test [ 14 ]. Some reports showed a high overall percent agreement using SP263 (96.3%, with a positive cut-off equal to 25% tumoral cells) and SP142 clones (94% with a cut-off equal to 5% of ICs) [ 15 , 16 ].…”

PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain

“…However, the use of PD-L1 as a biomarker is not exempt from hurdles; different testing systems have been used and different scoring and cut-off determinations have been suggested. Additionally, tumor heterogeneity in PD-L1 expression presents a challenge [24,25].…”

PD‐L1 and beyond: Immuno‐oncology in cytopathology

“…Consequently, recommendations for proper management of cytological material have been included in biomarker testing guidelines for patient selection in immuno‐oncology. For example, the Canadian Association of Pathologists‐Association Canadienne Des Pathologistes (CAP‐ACP) recommends that FDA‐approved or CE‐marked PD‐L1 IHC kits, validated for FFPE samples, be used for cytology samples only if they are processed according to the pre‐analytical conditions provided by the kit and the readout is compatible with the type of cytology samples 58 . For NSCLC cases, the International Association for the Study of Lung Cancer Pathology Committee (IASCL) requires that protocols for cytological materials be fully validated and submitted to quality‐control measures.…”