Dr. Camidge on Biomarker Combinations in NSCLC

David Ross Camidge, MD, PhD, professor, Division of Medical Oncology, Joyce Zeff Chair in Lung Cancer Research, School of Medicine, Division of Medical Oncology, University of Colorado, discusses biomarker combinations in non—small cell lung cancer (NSCLC).

The assumptions that physicians make for immunotherapy are much more exaggerated than for targeted therapy, says Camidge. If physicians find a mutation, they can be confident that it is going to turn into an abnormal protein and drive the cell and be sensitive to a tyrosine kinase inhibitor.

For immunotherapy, physicians assume that a high tumor mutational burden means more neoantigens are going to be presented on that patient's major histocompatibility complex (MHC). Physicians have to assume that they will be presented in a permissive immune environment, and that the relevant checkpoints are involved. Each of those assumptions are high-risk, explains Camidge.

To get around that, physicians have to combine biomarkers to reduce these assumptive risks, Camidge says. Physicians may be able to get better bioinformatics, but there are many remaining questions. Physicians do not yet know if mutations change the immune-acid sequence, whether neoantigens are going to present on a patient's MHC, or whether all mutations are equally immunogenic.