Programmed Death Ligand-1 and Tumor Mutation Burden Testing of Patients With Lung Cancer for Selection of Immune Checkpoint Inhibitor Therapies

The biomarker testing space has been complicated, however, by the proliferation of PD-Ll assays and scoring criteria that have evolved with individual therapies and often for different tumor types, some of which have received companion diagnostic (CDx) approvals by regulatory agencies such as the US Food and Drug Administration (FDA) and the Health Products and Food Branch of Health Canada.1 At the same time, for reasons of cost and access, PD-L1IHC antibodies and assays developed outside of the scope of randomized controlled trials (RCTs) have garnered widespread use,2 thus leading to confusion on the part of pathologists and clinicians about the best approach to biomarker testing to select patients for ICI therapy. [...]to most genomic biomarkers (eg, anaplastic lymphoma kinase [ALK], epidermal growth factor receptor [EGFR]), which tend to represent relatively stable and binary data points in a patient's tumor profile in treatment-naive patients, PD-L1 expression is dynamic and heterogeneous, complicating the choice of sample for testing.3-5 At the same time, there is ongoing interest in genomic biomarkers in immunotherapy-in particular, tumor mutation burden (TMB)-that may be used in conjunction with or independent of PD-L1 status. [...]questions regarding assay interchangeability persist. METHODS This evidence-based guideline was developed following the standards by the National Academy of Medicine.6 A detailed description of the panel composition, conflict of interest (COI) policy and systematic review methods used to create this guideline can be found in the online Evidence-Based Guidelines Development Methodology Manual (Methodology Manual).7 Guideline Panel The College of American Pathologists (CAP), in collaboration with the American Society of Clinical Oncology (ASCO), Association for Molecular Pathology (AMP), International Association for the Study of Lung Cancer (IASLC), Pulmonary Pathology Society (PPS), and the patient advocacy organization LUNGevity Foundation, convened a multidisciplinary expert and advisory panel to develop the guideline and approved the appointment of the members.