Dr. Herbst on Intriguing Immunotherapy Combinations in NSCLC

Roy S. Herbst, MD, PhD, Ensign Professor of Medicine and professor of pharmacology, chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; associate director for Translational Research, Yale Cancer Center; Disease Aligned Research Team (DART) Leader, Thoracic Oncology Program, Yale Cancer Center, discusses immunotherapy combinations that have potential in non-small cell lung cancer (NSCLC).

Combination immunotherapy makes sense in lung cancer, Herbst says. This is because though there is some activity with PD-1/PD-L1 inhibitors, this class of drugs are effective in approximately 20% of patients and most require additional therapy. Therefore, science-based combinations are critical, Herbst says.

Researchers should be exploring looking at resistance mechanisms and whether they progress on immunotherapy because they lack PD-1/PD-L1 expression and require an agent that targets another checkpoint expression, such as TIM-3 or LAG-3. Additionally, patients could have PD-L1 expression but they have myeloid-derived suppressor cells, T-regulatory cells, or macrophages. Personalizing therapy will help, Herbst says.

There are also methods to target the immune microenvironment, such as targeting CD73, the adenosine pathway, macrophages, bispecific antibodies, oncolytic viruses, and more. There needs to be more clinical trials of biomarkers to determine who is best to receive these types of agents, Herbst concludes.

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