Dr. Natale on the Utility of PD-L1 and TMB in Lung Cancer

Ronald B. Natale, MD, medical director, Clinical Lung Cancer Program and assistant clinical professor of medicine, Cedars-Sinai, discusses the utility of PD-L1 expression and tumor mutational burden (TMB) in lung cancer.

Approximately 40% to 50% of patients with stage IV non—small cell lung cancer benefit from an immune checkpoint inhibitor. While PD-L1 expression can provide insight into which patients are more likely to respond to immunotherapy, it’s not a perfect predictive marker, says Natale. For example, in the KEYNOTE studies, the addition of pembrolizumab (Keytruda) to chemotherapy led to a survival benefit in patients, irrespective of PD-L1 expression.

While TMB has not shown predictive value for immune checkpoint inhibitors, a subset of patients with TMB may benefit from this class of agents, says Natale. Currently, it is more difficult to test for TMB than it is to test for PD-L1 expression. The purity of the tumor and the proportion of normal cells in the specimen can skew results, explains Natale; that may be why some of the TMB studies have not proven to be as predictive as anticipated. As such, further biomarker research is needed to determine which patients should be treated with immune checkpoint inhibitors, concludes Natale.