Using FoundationOne®Tracker to Bring Clarity to Treatment Response

Foundation Medicine has transformed cancer care by providing patients, physicians and researchers with a deep understanding of the genomic alterations that drive cancer. FoundationOne Tracker, one of many tools in Foundation Medicine’s chest, is a product designed to detect very small amounts of circulating tumor DNA (ctDNA). It allows clinicians to determine whether their patients on therapy are responding to treatment. As such, it can provide objective insights into treatment response for patients with advanced cancer across all solid tumors.

Oncologists Use FoundationOne Tracker to Augment Imaging

Jerry Mitchell, MD, MBA, a medical oncologist, serves as the Director of Field Medical Oncology at Foundation Medicine. He brings to that role 18 years of experience providing direct patient care in a leading Midwest community practice. His drive to provide that support to patients is so great that, though now at Foundation Medicine, he continues to practice medicine. This blog is a summary of his perspective as a clinician, clinical researcher, and Director at Foundation Medicine.

Dr. Mitchell explains that, historically, oncologists have used computed tomography (CT) and positron emission tomography (PET) scans to monitor patient response to therapy. “CT scans and PET scans can be ambiguous,” says Dr. Mitchell. “They can be tough to read, and it can be difficult to understand how patients are responding to therapy. With immunotherapy there's also the complication of pseudo-progression where it looks on the CT or PET scan that the tumor is growing even though the patient is responding to therapy.” FoundationOne Tracker addresses these problems by providing another piece of objective data that oncologists can use to bring clarity to patient response to treatment and inform next steps in treatment.

ctDNA Levels Serve as an Indicator of Patient Response

FoundationOne Tracker uses ctDNA - a subset of the cell-free DNA circulating in plasma. While cell-free DNA includes both healthy tissue DNA and tumor-derived DNA, ctDNA comes only from tumors. “So, ctDNA, as most oncologists are familiar with, is a tool that's used in the advanced disease setting,” explains Dr. Mitchell. “Typically, oncologists will use ctDNA to try to find specific variants within the tumor that can be used to match with a therapy.” For example, in the case of a patient with advanced lung cancer, an oncologist may use liquid comprehensive genomic profiling in the hopes of identifying a variant that can be specifically matched with a therapy. FoundationOne Tracker analyzes ctDNA in a different way using tissue that has already been sequenced with FoundationOne CDx to identify 2-16 patient-specific variants, and then examining the ctDNA to determine if those variants are present or not present in the ctDNA. The goal of FoundationOne Tracker is not to match a patient to a therapy, but rather to determine, by quantifying ctDNA, whether the patient is responding or not to the treatment. Put simply, it answers the question: Is the ctDNA level going up, going down, or staying the same?

Oncologists may first use FoundationOne CDx to determine the baseline genomics of the cancer and determine the best course of treatment. They may also order FoundationOne Tracker to obtain a baseline ctDNA level pre-treatment, which may provide prognostic information.

Multiple Time Points Provide Valuable Information

“FoundationOne Tracker is intended to be used longitudinally with multiple time points throughout the course of treatment,” explains Dr. Mitchell. Oncologists typically order it on the same schedule as treatment so that the data align with an infusion schedule. Put simply, patients who are positive for ctDNA are likely to do worse and those who have no detectable ctDNA are likely to do very well and have a long disease-free interval.

Dr. Mitchell emphasizes that when it comes to monitoring treatment response, FoundationOne Tracker cannot replace imaging and serum markers. Instead, it is intended as a complementary tool that provides objective and quantitative data to inform understanding of response. Current evidence suggests that FoundationOne Tracker may be effective for patients with advanced solid tumors who are receiving immunotherapy.^[1]

When oncologists order FoundationOne Tracker, they receive an easy-to-read report stating either that there was no ctDNA present, meaning that the patient is responding to treatment, or that there is ctDNA present. If there is ctDNA present, then the report will include how much ctDNA is present. The oncologists who run FoundationOne Tracker serially over time will be able to see the ctDNA increasing or decreasing in a graph that plots ctDNA level (filled circle) over time. If ctDNA is not detected (empty circle), then the report will show a negative result, which could indicate the patient is responding to treatment.

IMpower131^[2]

Not only can oncologists use FoundationOne Tracker to monitor response to therapy, but there is the potential to adjust therapy based upon the results of FoundationOne Tracker. The subanalysis of IMpower131, presented in 2023 at the annual meeting of the American Society of Clinical Oncology (ASCO 2023) and published November the same year in Clinical Cancer Research, evaluated the change in ctDNA level from baseline to the end of four cycles of treatment. The IMpower131 study included three arms: atezolizumab+carboplatin+paclitaxel, atezolizumab+carboplatin+nab-paclitaxel, and carboplatin+nab-paclitaxel. The FoundationOne Tracker portion of the study focused on atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel.

The investigators found that the change in ctDNA over time was able to predict the efficacy of therapy and that, in patients who were ctDNA positive, an additional two cycles of therapy did not improve patient outcomes. This type of information, combined with imaging data, allows the oncologist to have a more informed discussion with the patient about what the results could mean for the specific patient. The study also found that FoundationOne Tracker was able to distinguish between patients who were expected to achieve a durable benefit from treatment from those who were at risk from disease progression. Moreover, the monitoring from FoundationOne Tracker delivered meaningful insight into treatment response even if oncologists began using it after treatment had been initiated. All told, the study found that FoundationOne Tracker was able to monitor ctDNA changes and predict patient outcomes.

FoundationOne Tracker is thus a simple and useful tool for more accurately monitoring and assessing treatment response. It makes it possible to monitor changes in ctDNA and obtain objective insights that can complement imaging. Dr. Mitchell concludes by emphasizing that Foundation Medicine continues to perform research to explore the ability of FoundationOne Tracker to monitor treatment response.

© 2024 Foundation Medicine, Inc. Foundation Medicine® and FoundationOne® are registered trademarks of Foundation Medicine, Inc.

FoundationOne®CDx is a qualitative next-generation sequencing based in vitro diagnostic test for advanced cancer patients with solid tumors and is for prescription use only. The test analyzes 324 genes as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies in accordance with the approved 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 test 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 the complete label, including companion diagnostic indications and important risk information, please visit www.F1CDxLabel.com.

FoundationOne®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.