Pathologists and medical oncologists know that when it comes to liquid biopsy blood tests to detect cancer, there is plenty of both hope and hype; however, these advances in the use of ctDNA analysis or liquid biopsy will be of interest to healthcare and oncology leaders seeking to provide personalized medicine to their patients
The desire to diagnose cancer as early as possible through noninvasive methods continues to drive liquid biopsy research and precision medicine strategies in oncology. Medical oncologists and other healthcare leaders may remember a particular announcement last fall. For perspective, leading clinical laboratory business journal The Dark Report highlighted a deal between cancer testing specialist NeoGenomics and liquid biopsy developer Inivata.
Inivata’s targeted minimal residual disease testing (MRD) was seen as an emerging and significant opportunity. The move, according to The Dark Report, followed NeoGenomics’ acquisition of Trapelo Health, a precision oncology decision-support software provider. Now, just over one year later, NeoGenomics reports that forthcoming data to be presented at the 2022 San Antonio Breast Cancer Symposium (SABCS) in December will support use of Inivata’s liquid biopsy assay across all types of early breast cancer in both the adjuvant (after treatment) and surveillance settings.
The findings add to Precision Medicine Institute’s noted of liquid biopsy research, collaborations, and advancements as 2022 approaches year-end. This is important as hospital executives anticipate possible directions for their precision medicine programs, precision oncology specifically, in the year ahead.
Liquid Biopsy Testing: ‘Clinical Potential’ for Detecting Recurrence of Breast Cancer
For a sense of how liquid biopsy has evolved since NeoGenomics’ acquisition of Inivata, a late November news announcement declared “clinical potential” for the company’s RaDaR assay for breast cancer. This is a sequencing test for the detection of MRD and recurrence. According to the company, findings from the c-TRAK TN trial combined with preliminary data from a long-term, prospective cohort study called TRACER may be significant toward the company’s ultimate goal of commercializing its breast cancer liquid biopsy assay in 2023.
“Our research shows that the RaDaR Assay is able to help follow therapy response in the neoadjuvant [first-step treatment] setting as well as identify patients at high risk of recurrence,” said David Cescon, MD, PhD, medical oncologist and clinical scientist in the Division of Medical Oncology and Hematology in the Department of Medicine at Princess Margaret Cancer Centre and University of Toronto, in the announcement.
Oncologists and other healthcare leaders may recall that MRD testing has been touted as “paradigm-shifting” for its potential impact in the patient cancer journey. MRD is understood to be the trace amounts of ctDNA that remain after surgery or other cancer treatment. The term ctDNA simply refers to DNA from a tumor that can be detected through a blood test or tissue-free liquid biopsy.
For several types of cancer, researchers continue to explore ctDNA analysis not only for MRD, but for identifying genetic alterations for use of targeted therapies, for those with advanced disease who cannot have a clinical biopsy for disease surveillance or management, and other points in cancer care, as liquid biopsy policy summaries and local coverage determinations (LCD) have explained.
An Emerging National Strategy for Liquid Biopsy Tests in the UK
While NeoGenomics and Inivata stake claims in the liquid biopsy market, others appear just as eager to be selected for precision medicine program strategies, especially those that involve scale. A major announcement in the United Kingdom indicated that the UK’s National Health Service (NHS) is pushing forward with the use of liquid biopsy tests for certain cancer patients. The Guardian reported this in January.
Inivata, which according to the company’s website, has R&D laboratories in Cambridge, UK, may be well-positioned to see its RaDaR assay used. However, The Royal Marsden, a specialist cancer hospital and National Institute for Health and Care Research (NIHR) Biomedical Research Centre for Cancer, reported in March that it will set up a state-of-the-art facility for in-house testing of liquid biopsies through a partnership with Guardant Health, which recently expanded its liquid biopsy testing from colorectal cancer to include breast and lung cancer as well, according to Guardant news from August.
ctDNA Liquid Biopsy Outlook
“Where next for ctDNA liquid biopsy in the NHS?” explained that breast, prostate, and ovarian cancers, as well as [non-small cell lung cancer] NSCLCs with mutations other than EGFR, are all cancers with targeted drugs available where ctDNA testing has been trialled. Those with metastatic cancers could also benefit from ctDNA profiling.
“The spread of a tumour to multiple, often inaccessible locations makes it difficult to obtain a representative solid biopsy sample, which can limit therapy options. There are now ambitions to expand ctDNA testing to patients with these cancer types, to allow greater access to targeted therapies when solid biopsies are infeasible,” stated the related University of Cambridge PHG Foundation article.
In yet another development, there is also the possibility of personalizing chemotherapy for colon cancer if tumor DNA is present in the bloodstream. If promises play out, this discovery will enable a precision medicine approach for certain types of colon cancer where unnecessary chemotherapy can be harmful, but failure to start chemotherapy when necessary can be even more harmful.
Collaborative, International Study Targets Stage II Colon Cancer
The discovery comes out of a collaborative study conducted by researchers from Johns Hopkins Kimmel Cancer Center in Baltimore and the Walter and Eliza Hall Institute of Medical Research (WEHI) in Parkville, Australia. The study adds to previous research that explored the clinical implications of ctDNA. As the researchers wrote in their opening of the related New England Journal of Medicine article, “The role of adjuvant chemotherapy in stage II colon cancer continues to be debated.” Stage II colon cancer can be difficult to correctly treat using chemotherapy.
“Stage II colon cancer presents a unique challenge,” explained Anne Marie Lennon, MBBCh, PhD, in a Johns Hopkins Medicine news release from June. Lennon is a professor of medicine and the director of the division of gastroenterology and hepatology at Johns Hopkins. “In stage I colon cancer, patients do not receive chemotherapy because their prognosis for survival is over 90%. The risk of discomfort and toxicities from the therapy outweigh the benefits it can provide. On the other hand, every stage III colon cancer patient currently receives chemotherapy because the risk of relapse is high.”
In this study, the researchers used ctDNA to help solve this problem, ultimately finding that patients with stage II colon cancer who had detectable ctDNA should receive chemotherapy to help reduce the risk of metastasis of the cancer, while those who did not have detectable ctDNA were at a much lower risk of metastasis and therefore could avoid the potential dangers of chemotherapy.
“Previous studies have theorized that ctDNA measurements might be useful in guiding patient management, and this study provides real-world clinical evidence that supports these theories,” said Bert Vogelstein, MD, professor at Johns Hopkins Medicine and co-author of the study.
Pathologists and medical oncologists know that when it comes to liquid biopsy tests to detect cancer, there is plenty of both hope and hype. However, these advances in the use of ctDNA analysis or liquid biopsy will be of interest to healthcare and oncology leaders seeking to provide personalized medicine to their patients. As more evidence is generated by these and other institutions, new precision medicine treatments and interventions will come.
—Liz Carey, Caleb Williams