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20 Years of Profound Progress in NSCLC Deserves a Diagnostics Portfolio Without Compromise

Precision medicine has transformed the way we view, approach, diagnose and treat non-small cell lung cancer (NSCLC). Transformation has been achieved in such a short space of time because precision medicine is its own engine of progress: a feedback loop where molecular testing and targeted treatment not only improve outcomes for patients in the clinic, but also provide vital insights that further deepen our understanding of tumor biology and fuel the innovation that delivers the next generation of treatments.

For decades, lung cancer was a cancer that seemed unbeatable. Five-year survival rates were practically immovable, only rising from 10.7% in 1970 to nearly 16% by the early 2000s,1 in stark contrast to many other cancers.2 Since the early 2000s, survival rates have continued to steadily increase, reaching 25% in 2022.3

The arrival of the new millennium was a turning point in lung cancer. The identification of EGFR gene mutations as oncogenic drivers in patients with non-small cell lung cancer (NSCLC) was the catalyst for two decades of unparalleled progress, ushering in a new era of targeted treatment options and advancements in comprehensive diagnostic testing options for NSCLC.

A turning point for lung cancer outcomes

New targetable molecular alterations are discovered on a regular basis. Treatments that target alterations in the EGFR, ALK, PI3K/AKT/mTOR, RAS-MAPK, RET, MET, BRAF, and NTRK/ROS1 pathways are now available in the clinic.4

For NSCLC without targetable drivers, immune checkpoint inhibitors (ICIs) are now a mainstay of therapy. Checkpoint inhibitors, including CTLA-4 inhibitors and those that target the programmed-death ligand 1 (PD-1/PD-L1), inhibit the regulatory pathways that control the activation of tumor-infiltrating T cells. This means the full power of the immune response can be directed at the tumor.

Without advances in genomic testing technology, the new array of targeted treatments would not exist, and it is now the standard of care to perform biomarker testing when NSCLC is diagnosed to inform the treatment strategy.5,6

Advocacy organizations are raising awareness and providing education on the importance of biomarker testing and the treatment options they can help identify for patients. Hear more from Courtney Granville, Ph.D, M.S.P.H., Chief Scientific Officer at GO2 for Lung Cancer, on this important topic:

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A new treatment landscape of hope and complexity

For patients, this wealth of potentially effective options brings hope of improved outcomes and significant reductions in mortality—it also makes for a very different conversation at diagnosis.

For healthcare providers, navigating the complexity of the treatment landscape is increasingly challenging and the growing number of testing options adds yet another layer of complexity.

As an oncologist, I want to have absolute confidence that the diagnostic test I have chosen has delivered all the knowledge and insights that I need to make the right treatment decision for my patients. 

A portfolio based on over a decade of leadership

Foundation Medicine has long been at the forefront of change in precision medicine and has an unmatched understanding of what defines excellence in biomarker testing. We have channeled this knowledge and expertise into creating a high-quality diagnostics portfolio that delivers the highest level of confidence for NSCLC patients.

Foundation Medicine has more FDA-approved companion diagnostic indications for NSCLC than any other testing company,7  and our portfolio of tissue- and liquid-based comprehensive genomic profiling (CGP) tests each detect all 11 guideline-recommended genes for advanced NSCLC.8,9,10 In addition,  FoundationOne®CDx11 is approved to be used as a companion diagnostic (CDx) to identify patients eligible for adjuvant therapy with two NSCLC medicines.  And, Foundation Medicine offers an FDA-approved CGP test, with the option to add tissue-informed ctDNA monitoring,7 with FoundationOne®Tracker.12

Another important advance in recent years has been the introduction of blood-based genomic profiling, also referred to as liquid biopsy. For many patients with advanced NSCLC, getting a tissue biopsy is not feasible due to the patient’s health, so liquid biopsy has unlocked the power of precision medicine for many more patients through a simple blood draw.

However, choosing liquid has traditionally meant compromising on the level of certainty that accompanies the results. Liquid biopsy relies on the tumor shedding enough DNA into the blood to enable accurate and reliable detection. So, in the case of a negative liquid biopsy result, it is recommended to reflex to tissue-based testing to avoid potentially missing important molecular alterations. This adds time, complexity and cost to the testing process and is not possible for many patients.

Recognizing this barrier, Foundation Medicine enhanced the capabilities of our liquid biopsy test. FoundationOne®Liquid CDx is the only CGP liquid biopsy to report ctDNA tumor fraction—for greater confidence in negative results.7,13 Our ctDNA tumor fraction value accounts for multiple inputs – aneuploidy, variant allele frequency (VAF), fragment length information, clonal hematopoiesis predictions (CH), and known tumor-associated alterations— to measure the amount of ctDNA in a sample. When ctDNA tumor fraction is high (≥1%), detection of drivers like EGFR, ALK, RET, and ROS1 is highly concordant with FoundationOne CDx. In contrast, when ctDNA tumor fraction is low and no driver is detected by FoundationOne Liquid CDx, follow-up tissue testing is more likely to detect additional drivers. VAF can tell a provider the relative frequency of genomic alterations in a sample, but ctDNA tumor fraction supports provider decision-making regarding reflex testing or treatment with standard of care.14

The most recent addition to our portfolio of diagnostic tests provides an additional element of certainty that every base has been covered through testing. While most fusions, which are a rare type of alteration that we can see in tumors, can be detected through DNA sequencing, there are a small number of fusions that can only be detected through RNA sequencing.  FoundationOne®RNA15 is a tissue-based RNA sequencing test for fusion detection that can now be added to a FoundationOne CDx order to provide another layer of sophisticated fusion detection in 318 genes through RNA sequencing that can be chosen as an option for certain patients when medically necessary. It does not require additional tissue and is incorporated into the FoundationOne CDx report to avoid additional patient impact and simplify decision making for health care providers.

Wrapped around our technology is the additional confidence provided due to the standards of quality we bring to our products, the convenience of our integrations with electronic medical records, flexible and clear result reporting, and the breadth of coverage and access we have achieved for patients.

The transformation we have seen in lung cancer is an incredible achievement, and we are unwaveringly committed to continued innovation in our portfolio of tests to advance the treatment landscape even further.


1Lu T, Yang X, Huang Y, et al. Trends in the incidence, treatment, and survival of patients with lung cancer in the last four decades. Cancer Manag Res. 2019;11:943-953.    

2Jemal A, Clegg LM, Ward E, et al . Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer. 2004:101: 3-27.

3American Lung Association. State of Lung Cancer. 2022. Accessed May 8, 2024.

4American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer. Updated April 29, 2024. Accessed May 2, 2024.

5NCCN Guidelines for Patients. Metastatic Non-Small Cell Lung Cancer. V3.2023. ©2023 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed May 2, 2024. To view the most recent and complete version of the guidelines, go online to

6NCCN Guidelines for Patients. Early and Locally Advanced Non-Small Cell Lung Cancer. V3.2023. ©2023 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed May 2, 2024. To view the most recent and complete version of the guidelines, go online to

7Data on File, Foundation Medicine, Inc. 2024

8NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer. V.1.2024. ©2024 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed May 2, 2024. To view the most recent and complete version of the guidelines, go online to

9Foundation Medicine, Inc. FoundationOne®CDx Technical Information. Accessed May 2, 2024.

10Foundation Medicine, Inc. FoundationOne® Liquid CDx Technical Information. Accessed May 2, 2024.

11FoundationOne®CDx and FoundationOne®Liquid CDx are qualitative next-generation sequencing based in vitro diagnostic tests for advanced cancer patients with solid tumors and are for prescription use only. FoundationOne CDx utilizes FFPE tissue and analyzes 324 genes as well as genomic signatures. FoundationOne Liquid CDx analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes. The tests are companion diagnostics to identify patients who may benefit from treatment with specific therapies in accordance with the therapeutic product labeling.  Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the tests does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy for testing with FoundationOne CDx when archival tissue is not available which may pose a risk. Patients being considered for eligibility for therapy based on detection of NTRK1/2/3 and ROS1 fusions should only be tested if tissue is unavailable. Patients who are tested with FoundationOne Liquid CDx and are negative for other companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and important risk information, please visit and

12FoundationOne®Tracker is a clinical test performed exclusively as a laboratory service.  This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA).   FoundationOne Tracker is a personalized assay for oncology that is based on patient-specific somatic variants (substitutions and short insertions/deletions) identified from baseline tumor tissue testing and used to detect and longitudinally measure plasma circulating tumor DNA (ctDNA) abundance as a biomarker for tumor burden. Treatment decisions are the responsibility of the treating physician. ctDNA detection sensitivity may be limited if blood collection occurs within two weeks of surgery or while a patient is on therapy. A negative test result does not definitively indicate the absence of cancer. This test is not designed to detect or report germline variation, nor does it infer hereditary cancer risk for a patient. This test is designed to detect ctDNA from the assayed tumor only; new primary tumors will not be detected. This test is expected to have limited sensitivity in some cancer types due to limited ctDNA shed.

13Foundation Medicine’s ctDNA tumor fraction is a determination of the amount of circulating tumor DNA as a fraction of total cell free DNA in a blood sample that accounts for aneuploidy, variant allele frequency, fragment length information, clonal hematopoiesis predictions and known tumor-associated alterations. ctDNA tumor fraction is reported as a laboratory professional service which has not been reviewed or approved by the FDA

14Rolfo CD, Madison R, Pasquina LW. Utility of ctDNA Tumor Fraction to Inform Negative Liquid Biopsy (LBx) Results and Need for Tissue Reflex in Advanced Non-Small Cell Lung Cancer(aNSCLC). J Clin Onc. 2023; 41(16):9076-9076. DOI: 10.1200/JCO.2023.41.16_suppl.9076.

15FoundationOne®RNA is a laboratory developed test that was developed and its performance characteristics determined by Foundation Medicine. FoundationOne RNA has not been cleared or approved by the U.S. Food and Drug Administration. FoundationOne RNA is a test for solid tumors which utilizes RNA sequencing to interrogate 318 cancer-related genes to capture gene fusions and rearrangements. A negative result does not rule out the presence of an alteration. Genomic findings are not prescriptive or conclusive for labeled use of any specific therapeutic product.

May 28, 2024 Mia Levy, MD, PhD Chief Medical Officer, Foundation Medicine

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