Help Identify More Eligible Patients

Foundation Medicine Patient
Immunotherapy Percentage

of patients who test negative for PD-L1 by IHC have MSI-high or TMB-high status, which may help inform immunotherapy decisions.6

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One Partner for All

Foundation Medicine Is Your Biomarker Resource for Cancer Immunotherapy Information

Comprehensive genomic profiling with FoundationOne®CDx, FoundationOne®Liquid and FoundationOne®Heme can deliver insights into relevant cancer-related genes and measure other important clinical biomarkers that may be associated with immunotherapy.

Our tests can help physicians better identify patients who may be more likely to benefit from immunotherapy by providing all relevant biomarkers from a single vendor.

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Relevant Biomarkers

JUMP TO BIOMARKER SUMMARY

Tumor Mutational Burden (TMB)

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TMB is a genomic biomarker that quantifies the frequency of somatic mutations in a patient’s tumor. Currently FoundationOne CDx and FoundationOne Heme report TMB scores as High, Intermediate, Low and Undetermined. The selection of these classifications was based on a retrospective analysis of our genomic data across tumor types.10 As TMB is a quantitative biomarker, current clinical trials are assessing therapeutic response at various cut-off levels in different tumor types.

TMB-high correlates with higher neoantigen expression, which helps the immune system recognize tumors.5 It has been detected across numerous tumor types and has been associated with improved response rate and prolonged progression-free survival for patients on immunotherapy.10,11

TMB expands the population of patients who can be considered candidates for immunotherapy beyond standard PD-L1 testing.10,12

Comprehensive Genomic Profiling Concordance with Whole Exome Sequencing

Foundation Medicine has established concordance of its comprehensive genomic profiling tests with WES, and has demonstrated clinical utility of TMB to effectively predict immunotherapy response and survival for more than 1,300 patients across 6 separate studies representing 21 different tumor types.5,10,12

FoundationOne CDx and FoundationOne Heme provide TMB status on all reports without any additional tissue, test requisition form, or cost.

Microsatellite Instability (MSI)

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MSI is a genomic biomarker that is a signature of deficient mismatch repair (dMMR) which results in an abnormally high frequency of genetic mutations.13 MSI-high status correlates with higher neoantigen expression which helps the immune system recognize tumors. Identification of MSI-high status is part of an FDA-approved indication for pembrolizumab, an immunotherapy drug that has expanded its approval across all solid tumor types in MSI-high patients when previous therapies have failed.14 High MSI levels have been detected in more than 20 types of solid tumors, thus underlining the importance of testing all patients for this key biomarker.5,15

MSI-High Longtail Plot

Foundation Medicine’s hybrid-capture, next-generation sequencing (NGS) methodology has high sensitivity and specificity for clinical MSI-high testing across tumor types.16

FoundationOne CDx, FoundationOne Liquid,* and FoundationOne Heme provide MSI status on all reports without any additional tissue, test requisition form, or cost.

*On FoundationOne Liquid, MSI is only reported as either MSI-high or MSI-undetermined

Programmed Death Ligand-1 (PD-L1)

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PD-L1 is a protein biomarker that is strongly associated with immune system suppression.17 Positive PD-L1 immunohistochemistry (IHC) can indicate that a patient will be more likely to respond to immunotherapy. However, the variability of this biomarker highlights the need for additional tools to predict which patients may be candidates for immunotherapy.4

By combining PD-L1, TMB, and MSI testing, you can be more confident that you are considering all viable treatment options for your patients.

Looking Beyond PD-L1

PD-L1 is available through Foundation Medicine on the same test requisition form as FoundationOne CDx and FoundationOne Heme with minimal additional tissue and no added wait time.

DOWNLOAD OUR IHC SPECIMEN INSTRUCTIONS

Biomarker Summary

Foundation Medicine’s portfolio provides reliable and accurate measurements of TMB and MSI by comprehensive genomic profiling and PD-L1 expression by IHC. Leverage our tests to comprehensively help inform immunotherapy treatment options for your patients.

Definition

TMB is a genomic biomarker that quantifies the frequency of somatic mutations in a patient’s tumor. Increasing TMB correlates with increased numbers of neoantigens, which helps the immune system recognize tumors.

At Foundation Medicine

Reported As*

  • TMB-High: ≥20 Muts/Mb
  • TMB-Intermediate: 6-19 Muts/Mb
  • TMB-Low: ≤5 Muts/Mb
  • Cannot Be Determined: An accurate TMB score was unable to be calculated.

*These classifications were based on a retrospective analysis of our genomic data across tumor types. Current clinical trials are assessing therapeutic response at various quantitative cut-off levels in different tumor types.


  1. Márquez-Rodas et al. Immune checkpoint inhibitors: therapeutic advances in melanoma. Ann Transl Med. 2015;3(18):267.
  2. Wolchok et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122-33.
  3. Lipson et al. Antagonists of PD-1and PD-L1 in Cancer Treatment. Seminars in Oncology. 2015;42(4):587-600.
  4. Kerr KM, Hirsch FR. Programmed Death Ligand-1 Immunohistochemistry: Friend Or Foe? Arch Pathol Lab Med. 2016;140:326–31. doi: 10.5858/arpa.2015-0522-SA.
  5. Chalmers ZR, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9:34. doi: 10.1186/s13073-017-0424-2.
  6. Data based on Foundation Medicine experience as of June 2017.
  7. Samstein RM. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics 2019;51:202-206.
  8. Stenger M. Pembrolizumab in MSI-H or dMMR Solid Tumors: ‘First Tissue/Site-Agnostic’ Approval by FDA. The ASCO Post [Internet]. 2018 Feb 10 [cited 2019 Jan 2]. Available from: www.ascopost.com/issues/february-10-2018/pembrolizumab-in-msi-h-or-dmmr-solid-tumors-first-tissuesite-agnostic-approval-by-fda/
  9. Center for Drug Evaluation and Research. (2019, February 06). Approved Drugs - Hematology/Oncology (Cancer) Approvals & Safety Notifications. Retrieved February 07, 2019, from www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm
  10. Goodman AM, et al. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017;16(11):2598-608. doi: 10.1158/1535-7163.MCT-17-0386.
  11. Carbone D, et al. First-line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017;376:2415-26. doi: 10.1056/NEJMoa1613493.
  12. Internal Data on File.
  13. Kim TM, Laird PW, Park PJ. The Landscape of Microsatellite Instability in Colorectal and Endometrial Cancer Genomes. Cell. 2013;155(4):858-68. doi: 10.1016/j.cell.2013.10.015.
  14. Keytruda (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2014.
  15. Cortes-Ciriano I, et al. A molecular portrait of microsatellite instability across multiple cancers. Nature commun. 2017;8:15180.
  16. Hall MJ, et al. Evaluation of microsatellite instability (MSI) status 11,573 diverse solid tumors using comprehensive genomic profiling (CGP). Poster session presented at: 2016 ASCO Annual Meeting; 2016 June 3-7; Chicago, IL.
  17. Xu-Monette ZY, et al. PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response? Front Immunol. 2017;8:1597. doi:10.3389/fimmu.2017.01597.