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David L. Rimm, MD, PhD, professor of pathology and of medicine, director of pathology tissue services, director of translational pathology, Yale Cancer Center, discusses alternatives to PD-L1 testing to predict response with checkpoint inhibitors in lung cancer.
Around 10% of patients who are PD-L1 negative still show some benefit from a PD-1 inhibitor. A test is needed to identify those patients, says Rimm. There are a number of other potential approaches that are being considered, including genomic approaches, neoantigen-type approaches, and other protein or alternative microenvironment-type approaches.
Genomic and neoantigen approaches are less likely to succeed, say Rimm. A more sensitive, less specific test is preferred, because it is better to treat a few patients that may not respond than it is to be too specific and rule out those who may benefit from an immunotherapy, he says.
One promising approach is to look at tumor-infiltrating lymphocytes or other cells within the environment of the tumor that may not actually be expressing PD-L1, but are the cells that actually kill the tumor.