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Quantum Leaps for Quantitative Markers

Recent clinical data demonstrate the enormous impact that quantitative genomic biomarkers like tumor mutational burden (TMB) have made on the treatment landscape, especially in immunotherapy. TMB was a major topic at the recent American Association for Cancer Research (AACR) Annual Meeting, standing alongside data readouts from pivotal clinical trials. Moving forward, more data will help us further understand the role of TMB and other biomarkers, and could lead to major research advances in precision oncology.

Prospective Data: A TMB Milestone

The predictive power of TMB has been suggested in several cancer types using retrospective studies. These data sets provide a solid foundation on which to build our hypotheses around TMB and its association with response to checkpoint inhibitor immunotherapy. They have ultimately led to where we are today, with the first major prospective clinical trial using TMB recently meeting a co-primary endpoint.

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The transition from retrospective to prospective data is a huge step forward that opens the door to an even greater understanding of TMB. While these data are exciting, they also require accurate interpretation of the results to ensure that we move the field forward in a rational way and help the community understand the value and potential impact of such biomarkers on clinical care.

A Path to Improving Outcomes for Immunotherapy

The pace of progress in immunotherapy is astounding. Recent clinical data, especially in lung cancer, have shown tremendous results for many patients. However, we continue to struggle to identify which patients are likely to benefit and, just as importantly, which are not. Having this capacity is important because immunotherapy can be associated with high cost and toxicity.

TMB has been shown to help us identify patients who would be good candidates for immunotherapy across a growing number of cancer types. Foundation Medicine and its collaborators recently published a study of more than 100,000 human cancer genomes that identified 20 tumor types, affecting eight tissues, in which greater than 10 percent of patients had high TMB. These results could have a significant impact on improving outcomes for immunotherapy. Another recent study showed that 151 immunotherapy-treated patients with high TMB across 21 different cancer types had better outcomes compared to patients with low TMB.

It is important to note here that while quantitative and reliable, TMB tests need to establish harmonization. To that end, we are part of a consortium whose main goal is to standardize the definition and analytic validation requirements for TMB, and to provide reference standards that ensure consistency of this measurement across separate platforms.

The Future of TMB

The potential for TMB is greater than ever. As comprehensive genomic profiling and TMB are integrated more routinely in clinical care, the field will acquire more data and gain a deeper understanding of cancer genomics. We look forward to presenting data at this year’s American Society of Clinical Oncology Annual Meeting that continue to uncover the predictive power of TMB and other biomarkers in different cancer types. Alongside, I believe that tools like our FDA-approved FoundationOne CDx assay, which includes both TMB and microsatellite stability (MSI) in every report and is covered by Medicare for eligible patients, will be important drivers of this progress.

Collaboration will become even more essential. Foundation Medicine has partnered with biopharma companies to optimize and accelerate biomarker-driven research, which has the potential to streamline regulatory and approval processes and thus broaden availability of treatments for patients.

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Foundation Medicine is also advancing a blood TMB (bTMB) assay, which extends the opportunities for precision treatment approaches to patients for whom a tissue biopsy may not be feasible. We’re working to establish the clinical utility of this assay in clinical trials, with the ultimate goal of providing this as an important new option to patients.

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Foundation Medicine has long pioneered the advancement of TMB, and the field has made remarkable progress. It is poised to make even more significant leaps forward as we pursue the full potential of precision medicine.