Tumor Mutational Burden (TMB) Measured by FoundationOne

Today, Foundation Medicine and our collaborators presented data at the American Society of Clinical Oncology (ASCO) annual meeting demonstrating that tumor mutational burden (TMB) measured by FoundationOne comprehensive genomic profiling (CGP) is a potentially more sensitive method for identifying responders to checkpoint inhibitor-based therapeutic approaches than microsatellite stability (MSI) status.

There is a critical need for an efficient and cost-effective method of identifying biomarkers that can predict a response to certain therapies. In colorectal cancer, MSI status is used to evaluate whether a tumor will respond to certain therapies and tumors that have been assessed as microsatellite instable (MSI-H), which also correlates with high neoantigen burden, may respond well to therapies that target either the PD-1 or PD-L1 proteins. Additionally, TMB has been shown to correlate well with the number of neoantigens found in a tumor, and therefore could be a potential predictive biomarker.

The study titled, “Tumor Mutational Burden as a Potential Biomarker for PD1/PD-L1 Therapy in Colorectal Cancer,” assessed the TMB levels of 2,013 clinical samples from patients with colorectal cancer using comprehensive genomic profiling with FoundationOne and compared these to MSI status. Within all 2,013 CRC cases sequenced by Foundation Medicine, 100 percent of MSH-high patients were also TMB-high. Nearly 22 percent of MS-stable CRC cases were TMB-high. Further, CRC cases, which were MSS/TMB-H, harbored a gene signature consistent with MSI-H cases, including enrichment of MSH2, POLE and POLD1.
These findings suggest that measuring tumor mutational burden using FoundationOne may provide a more effective solution to assist physicians in identifying a larger percentage of CRC patients who might respond well to therapies that target either the PD-1 or PD-L1 proteins.