Professional Societies Introduce New Evidence-Based Guidelines on Testing Immunotherapy Biomarkers in NSCLC

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The College of American Pathologists in collaboration with the International Association for the Study of Lung Cancer, the Pulmonary Pathology Society, the Association for Molecular Pathology, and the LUNGevity Foundation have developed evidence-based recommendations on the use of certain biomarkers to help determine which patients with non–small cell lung carcinoma (NSCLC) may benefit from immune checkpoint inhibitors, according to new guidelines published by Sholl et al in the Archives of Pathology & Laboratory Medicine.


“Clinical trials have demonstrated that drugs that block PD-1 and PD-L1 lead to significant improvements in both response and survival relative to conventional cytotoxic chemotherapy for patients with advanced-stage NSCLC,” emphasized lead guideline author Lynette Sholl, MD, FCAP, of Brigham and Women’s Hospital.

“Many [patients with NSCLC] may benefit from therapies that can harness the immune system, including anti–PD-1 or PD-L1 therapies. However, the benefit of these therapies is not universal, and clinically validated biomarkers that can help predict response include PD-L1 expression and proposed tumor mutational burden,” explained senior guideline author Larissa Furtado, MD, FCAP, of St. Jude Children’s Research Hospital.

Overview of the New Evidence-Based Guidelines

The new guidelines were driven by the production of PD-L1 assays and scoring criteria that have evolved with individual therapies. Simultaneously, PD-L1 immunohistochemical antibodies and assays developed outside the scope of randomized controlled trials have garnered widespread use because of their cost and accessibility.

An expert panel recognized that the regulatory-approved diagnostics are clinically validated; therefore, their use was recommended. However, most laboratories may rely on laboratory-developed tests because of limited access to the full suite of approved clones and platforms as well as the increased cost of running companion diagnostic–labeled assays.

“To ensure patient access to PD-L1 testing, particularly at the local level, we endorse the use of [laboratory-developed tests] and validated PD-L1 [immunohistochemical laboratory-developed tests] following technical validation against one or more of the approved companion diagnostic PD-L1 assays,” Dr. Furtado indicated.

With six recommendations, the new guidelines provide data and details regarding the efficacy and utility of PD-L1 testing in patients with NSCLC.


“This guideline is intended to provide an overview of the clinical rationale for the use of PD-L1 and tumor mutational burden testing for patients with [NSCLC]. It highlights the technical challenges of PD-L1 testing and interpretation, including some of the complexities introduced by the development of divergent companion diagnostic PD-L1 tests for different immune checkpoint [inhibitor] therapies. It outlines the rationale for use of [tumor mutational burden] and the current limitations of this test for [patients with NSCLC],” concluded Dr. Furtado.

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