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Is KRAS Status Linked to Response to Immunotherapy for Advanced Lung Cancer?

By: Anna Nowogrodzki
Posted: Monday, June 21, 2021

KRAS variant status may affect response to immune checkpoint inhibitor monotherapy in patients with advanced non–small-cell lung cancer (NSCLC) who have high PD-L1 expression, according to a recent study. The researchers found that KRAS wild-type status was correlated with worse overall survival (13.6 months) with immune checkpoint inhibitors than KRAS variant status (21.1 months)—a difference not seen with chemoimmunotherapy. Charu Aggarwal, MD, MPH, of the Abramson Cancer Center, Philadelphia, and colleagues published their results in JAMA Oncology. The authors suggest further research to corroborate these data and determine how to use them for clinical treatment selection.

“These data suggest that chemoimmunotherapy might be favored over immune checkpoint inhibitor monotherapy for patients with KRAS wild-type with high PD-L1 expression,” the authors wrote. “There will be clinical implications for a large portion of patients with advanced lung cancer, as we learn more about this mutation and how other mutations may play a role in response,” Dr. Aggarwal commented in a Penn Medicine press release.

The study included 1,127 patients from the Flatiron Health database who had advanced nonsquamous NSCLC and a PD-L1 expression of 50% or more. Of these patients, 51% had KRAS variants, and 49% had KRAS wild-type disease. Patients were treated with either immune checkpoint inhibitor therapy alone or chemoimmunotherapy between January 2016 and May 2020.

When patients were given immune checkpoint inhibitors alone, wild-type KRAS status was associated with worse overall survival (13.6 months) than KRAS variants (21.1 months). Among patients with KRAS wild-type disease, there appeared to be a numerical difference in survival depending on the type of therapy received—13.6 months with immune checkpoint inhibitors compared with 19.3 months with chemoimmunotherapy—but this was not statistically significant. By contrast, when patients were given chemoimmunotherapy, there was no reported difference in overall survival by KRAS genotype.

Disclosure: The study authors’ disclosures may be found at jamanetwork.com.



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