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Predictor of Response Rates to Anti–PD-1 Therapies Across Cancer Types

By: Cordi Craig
Posted: Thursday, May 17, 2018

A strong relationship was observed between tumor mutational burden and objective response rate for anti–PD-1 therapy across multiple cancers, in an extensive literature review published in The New England Journal of Medicine. This study, led by Mark Yarchoan, MD, PhD, and colleagues at Johns Hopkins University, Baltimore, supports the efficacy of tumor mutational burden as an emerging biomarker of response to an immune checkpoint inhibitor.

“Our linear correlation formula can be used to make hypotheses with respect to the objective response rate in tumor types for which anti–PD-1 therapy has not been explored,” the investigators stated.

In the review, 27 tumor types or subtypes were identified for which objective response rate data were available. Response data were pooled based on tumor type from the largest published studies, and the authors used a validated genomic profiling assay to obtain the median tumor mutational burden for each tumor type.

A significant correlation existed between the tumor mutational burden and objective response rate. The authors determined that 55% of the variance in objective response rates could be explained by tumor mutational burden. Although a strong relationship exists between the two factors, different cancers varied in their response to therapy than would be predicted solely by mutational burden.

“Many different factors modulate the clinical response to an immune checkpoint inhibitor, but our findings highlight the strong relationship between the tumor mutational burden and the activity of anti–PD-1 therapies across multiple cancers,” Dr. Yarchoan and colleagues commented.



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