Evidence Grows for Tumor Mutational Burden as Predictor of Immunotherapy Success

Published: Thursday, Nov 29, 2018
Garrett Frampton, PhD

Garrett Frampton, PhD

An unmet need exists for biomarkers that can identify response to PD-1/PD-L1 blockade as well as other immunotherapies. Tumor mutational burden (TMB), a measure of the total number of somatic mutations per million bases of coding sequence in a tumor genome, has been shown in studies to predict response to immunotherapies in certain types of cancer and is being validated in clinical trials as a biomarker of response.

Results from studies have demonstrated that subsets of patients with high TMB exist across almost all cancer types and that assessing TMB through whole-exome sequencing or next-generation sequencing (NGS) can predict response to a range of different types of immunotherapy.

“[Results from] a recent phase III prospective study showed that high TMB was predictive of response to a frontline immunotherapy combination in patients with lung cancer,” said Garrett Frampton, PhD, senior director of cancer genomics research for Foundation Medicine in Cambridge, Massachusetts, which has developed solid and liquid tumor assays that test for TMB. “TMB is being studied in many other cancer types to better understand its predictive role. In the future, TMB has potential as a companion diagnostic for immunotherapy treatments,” Frampton told OncologyLive®.

In the study, investigators found that regardless of PD-L1 expression, in patients with non–small cell lung cancer (NSCLC) and high TMB, progression-free survival (PFS) was significantly longer with first-line nivolumab (Opdivo) plus ipilimumab (Yervoy) than with chemotherapy. The 1-year PFS among patients with high TMB was 42.6% with nivolumab plus ipilimumab versus 13.2% with chemotherapy. Median PFS was 7.2 months versus 5.5 months, respectively (HR, 0.58; 97.5% CI, 0.41-0.81; P <.001). The results were interpreted as a validation of the role of TMB as a biomarker for patent selection.1

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