Fast Five Quiz: Genetics of Non–Small Cell Lung Cancer

Daniel S. Schwartz, MD, MBA


February 03, 2021

Figure 1. Programmed cell death ligand 1 molecule.

One of the foundations of treatment for NSCLC is genetic testing to determine the genetic drivers of the disease. KRAS mutation is one of the most commonly mutated oncogenes. However, KRAS is a heterogeneous group and is not a stand-alone biomarker. PD-L1 expression and TMB are also major determinants in offering a personalized approach to NSCLC treatment options.

A major contributing factor to TMB is tobacco exposure, which is common in KRAS-mutated NSCLC. The higher the TMB, the better chance of benefit with immunotherapy.

Higher PD-L1 expression scores have been associated with better responses to immunotherapy, so some experts suggest that single-agent immunotherapy may be the best option for patients with KRAS-mutated NSCLC who have a PD-L1 expression score > 50%. However, identifying predictive biomarkers beyond PD-L1 have become a priority. The mutational landscape is but one determinant of sensitivity to PD-L1 blockade.

Although chemoimmunotherapy can be given to patients who have a PD-L1 expression score > 50%, it may not be necessary to achieve a favorable response. In contrast, patients with KRAS mutations tend to respond poorly to TKIs, making TKIs an unsuitable choice. Treatment options have been enriched by the development of immune checkpoint inhibitors, which confer positive results on NSCLC patients generally, including in those with KRAS-mutant NSCLC.

Learn more about factors associated with KRAS mutation.


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