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The Liquid Biopsy Trends Transforming Cancer Detection and Treatment

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Liquid biopsy is a less invasive approach compared to traditional surgical biopsies. By collecting a simple blood sample and analyzing circulating tumor DNA (ctDNA), cancer researchers and healthcare professionals can access a myriad of information about a patient’s tumor. Helping them gain insight into the genomic alternations driving the cancer, provide insight into how well an existing treatment is working or whether a potential treatment may be suitable for a specific patient.

We recently spoke with Prasanth Reddy, MD MPH CPE FACP, Vice President, Medical Affairs at Foundation Medicine to learn more about the latest developments in liquid biopsy. Prasanth discusses their recently launched liquid biopsy test FoundationOne® Liquid and its impact on oncology treatment decisions. He also highlights some of the data that was presented by Foundation Medicine at this year’s World Lung Congress.

LL: Could you highlight some of the latest liquid biopsy trends?

PR: In oncology, a liquid biopsy test analyzes circulating tumor DNA (ctDNA) in the blood to provide insights into the genomic alterations that may be driving a patient’s cancer and, in some cases can serve as an alternative to an invasive tissue biopsy. Patients with advanced solid tumors may benefit from this blood-based approach, which provides more options for patients who are unable to undergo an invasive tissue-based biopsy for a variety of reasons, including an instance where tissue is not available, additional tissue is too risky to obtain, and for monitoring for progression in certain clinical situations.

One exciting new development is the ability to use liquid biopsy to predict a patient’s response to cancer immunotherapy. ctDNA assays that report blood tumor mutational burden (bTMB) and microsatellite instability (MSI) are demonstrating potential as non-invasive predictors of immunotherapy response. MSI is already established as a pan-cancer biomarker of response to immunotherapy through the approval of pembrolizumab, and bTMB has shown potential to serve as a predictor of immunotherapy response in lung cancer. Thanks to these clinical advances, a simple blood test could be the blueprint to finding the correct path towards a patient’s personalized cancer treatment.

LL: During the World Lung Congress you launched FoundationOne® Liquid. What is FoundationOne Liquid and how might it influence oncology treatment decisions?

PR: FoundationOne® Liquid is a liquid biopsy test that enables comprehensive genomic profiling in patients unable to undergo an invasive tumor biopsy, or where tissue is unavailable, to help clinicians optimize and personalize treatment strategies for patients with advanced cancers. By analyzing ctDNA in a simple blood draw, FoundationOne Liquid uses next-generation sequencing (NGS) to analyze the four main classes of genomic alterations in 70 cancer-related genes, including homologous recombination deficiency (HRD) genes which could inform use of PARP inhibitors, to help guide therapy selection and suitability for clinical trials. It also reports MSI-high status, an indicator which may help inform immunotherapy treatment decisions. FoundationOne Liquid can also be used to complement prior tissue-based testing methods, providing results with longitudinal comparisons to previous Foundation Medicine test results. In addition, Foundation Medicine offers an option to automatically reflex to FoundationOne Liquid if tissue is insufficient for tissue-based testing.

FoundationOne Liquid test expands upon the previous version of our liquid biopsy test, FoundationACT®, and includes robust performance, expanded gene content, and simplified reporting.

LL: You had a strong presence at this year’s World Lung Congress. Could you touch on some of the company’s activities during this year’s event?

PR: At this year’s conference, Foundation Medicine presented tissue and blood-based comprehensive genomic profiling data as part of its efforts to advance biomarker-driven research and treatment.

  • In one study presented, comprehensive genomic profiling of both tissue and blood samples was used to identify MET rearrangements in non-small cell lung cancer (NSCLC). MET kinase fusions and MET kinase domain duplications have been observed as primary drivers and as acquired resistance mechanisms to ALK and EGFR inhibitors, and thus comprehensive genomic profiling (CGP) is important for detecting various classes of MET alterations to potentially inform treatment decisions.

  • In another study, a retrospective analysis of clinical, pathologic and molecular data from metastatic lung cancer patients presented at the University of California Davis molecular tumor board (MTB) demonstrated that the MTB was able to match a high percentage of patients to either targeted treatment or clinical trials with targeted therapies or immunotherapy.

Foundation Medicine also hosted a session on liquid biopsy titled “Implementing Liquid Biopsies into Clinical Practice: Challenges, Achievements and Progress” featuring presentations by Drs. Nir Peled (Sheba Medical Center), Ruben Cabanillas (Institute of Molecular and Oncological Medicine of Asturias) and Sai-Hong Ignatius Ou (University of California Irvine).

LL: Could you give us some insight into Foundation Medicine’s expanding portfolio of cancer genomics products?

PR: In addition to the recent commercial availability of the next-generation of our liquid biopsy test, FoundationOne Liquid, in April 2018, the U.S. Food and Drug Administration (FDA) granted a Breakthrough Device designation for a forthcoming version of our liquid biopsy test that will also include the genomic biomarker blood tumor mutational burden (bTMB). If approved, this test could be the first FDA-approved liquid biopsy test to incorporate multiple companion diagnostics (CDx) and multiple biomarkers to inform the use of targeted oncology therapies, including immunotherapies.

Additionally, Foundation Medicine and collaborators recently published a paper on bTMB supporting the ability of the company’s novel, investigational bTMB assay to help predict response to a checkpoint inhibitor immunotherapy in previously treated NSCLC patients. This bTMB assay is being prospectively evaluated in two Genentech studies: in the Phase III Blood First Assay Screening Trial (BFAST) as a companion diagnostic assay to validate bTMB as a non-invasive biomarker of response to first-line atezolizumab in advanced NSCLC patients, and in the single arm Phase II Blood First-Line Ready Screening Trial (B-F1RST) evaluating atezolizumab monotherapy in first-line NSCLC.

Prasanth Reddy, MD MPH CPE FACP, was speaking to Laura Elizabeth Lansdowne, Science Writer for Technology Networks.