Ronald B. Natale, MD, medical director of the Clinical Lung Cancer Program and assistant clinical professor of medicine at Cedars-Sinai, discusses the evolution of immunotherapy in advanced non–small cell lung cancer (NSCLC).

Over the past 2 years, the role of immunotherapy in NSCLC has evolved from approvals for second-line treatment in advanced stage IV disease. Since then, results from randomized clinical trials have demonstrated that both nivolumab (Opdivo) and pembrolizumab (Keytruda) are more effective than docetaxel, but with those data, the immune checkpoint inhibitors have quickly moved into the first-line setting, explains Natale.

The first group of studies in this field were done with immune checkpoint inhibitors versus standard first-line chemotherapy. Results have indicated that, in patients with a high tumor proportion score of PD-L1, which constitutes about 25% to 30% of the patient population,single-agent pembrolizumab was superior to standard platinum-based chemotherapy in those with squamous or NSCLC, concludes Natale.

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Ronald B. Natale, MD, discusses the evolution of immunotherapy in advanced non–small cell lung cancer.

Dr. Natale on the Evolution of Immunotherapy in NSCLC

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.

Ronald Natale, MD

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Dr. Natale on the Evolution of Immunotherapy in NSCLC

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