The advent of blood tests that can detect multiple cancers at early stages will not only reshape how the disease is diagnosed but will bring about a major shift in the delivery of care, according to research leaders at the European Society for Medical Oncology congress 2022.
By capturing evidence of tumor DNA with a simple blood draw, companies such as Grail, Exact Sciences and others are setting the stage for a future where many more people will be screened for cancer—with positive results coming at times when treatments could potentially be the most successful.
“It is a duty of professional societies like ESMO to raise awareness of the fact that within the next five years, we will need more doctors, surgeons and nurses, together with more diagnostic and treatment infrastructure, to care for the rising number of people who will be identified by multi-cancer early detection tests,” Fabrice André, director of research at Gustave Roussy Cancer Centre, said in a release.
“We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests, for example in the diagnosis and treatment of people with pancreatic and other cancers that are usually diagnosed at a much later stage,” said André, who this year is serving as scientific co-chair of ESMO’s annual congress in Paris and was elected future president of the society for 2025 and 2026.
At the conference, Grail—which for over a year has been the target of a beleaguered multibillion-dollar acquisition deal, pursued by the DNA sequencing giant Illumina—presented the final results of its interventional screening study that aimed to track the test’s performance in real-world clinical practice.
The company evaluated two versions of its Galleri test—which launched in the U.S. last year, designed to spot the signs of as many as 50 cancers from different organs—and found that the addition of a multi-cancer early detection test, or MCED, to standard care could more than double the number of cases discovered.
Dubbed Pathfinder, the single-arm trial showed that 71% of the people who did receive positive results had types of cancer that currently have no routine screening tests available, according to the company.
“In fact, Galleri detected more cancers than all U.S. Preventive Services Task Force-recommended standard single cancer screenings combined,” Grail’s chief medical officer, Jeffrey Venstrom, M.D., said in the company’s release. “These included stage I cancers of the liver, small intestine and uterus and stage II pancreatic, bone and oropharyngeal cancers.”
Previously, studies of multi-cancer early detection tests have relied on archived blood samples or groups of participants already known to have cancer or not have cancer. This Pathfinder analysis prospectively screened 6,662 people ages 50 and up, an age group that may have an elevated risk for the disease.
About 0.9%, or 92 participants, had signs of tumor DNA identified in their bloodstream, and 35 people had their cancers confirmed in follow-up tests. Nearly half, or 48%, of the cancers were newly developed, and found in stages 1 and 2.
“This is particularly notable given the Pathfinder population was heavily screened with higher-than-average rates for mammography, colonoscopy and low-dose CT lung scans,” Venstrom said.
The study used an earlier version of Galleri as well as an updated test that had been fine-tuned to reduce the number of positive results for pre-malignant blood conditions, which can be common. Researchers first completed the study with the earlier test, before retesting collected samples using the second version. According to Grail, the test had a rate of false positives of less than 1%.
“The results are an important first step for early cancer detection tests because they showed a good detection rate for people who had cancer and an excellent specificity rate for those who did not have cancer,” said the study’s senior author, Deb Schrag, M.D., chair of the department of medicine at Memorial Sloan Kettering Cancer Center.
“In people with a positive test, it took less than two months to confirm the diagnosis if they had cancer and it took a bit longer if they did not have cancer, primarily because physicians opted to perform imaging studies and then repeat them a second time several months later to investigate the possibility of a cancer diagnosis,” Schrag said.
The median time it took for people who received a positive test result to receive a definitive confirmation was 79 days. Meanwhile, the blood test’s ability to track a cancer signal back to its particular organ of origin was rated with 97% accuracy.
“An important finding was that few participants with a false positive screening test required multiple invasive procedures such as endoscopies and biopsies,” she added. “This finding should help to allay concerns that these tests could cause harm by generating unnecessary procedures in people who are well.”
The Grail test is also being studied through the U.K.’s National Health Service, screening at least 140,000 people over the age of 50 who have no suspicious signs of cancer, alongside a group of 25,000 over age 40 who may have symptoms of the disease.
Elsewhere at ESMO’s annual congress, Exact Sciences showed off validation data exploring four different biomarkers used by its multi-cancer early detection test, which delivered a false-positive rate of 1.8%. The company’s test also correctly identified positive results 61% of the time.
By analyzing genetic mutations, changes in the DNA structure, the presence of certain proteins and changes in the number of chromosomes—a combined approach developed through work with Johns Hopkins University and the Mayo Clinic—the study included cancers from 11 organ sites with no recommended screening tests today and 15 sites in total, including breast, bladder, colon, esophageal, kidney, liver, lung, ovarian, pancreatic, prostate, stomach and uterine cancers, as well as the blood-based multiple myeloma, myelodysplastic syndrome and non-Hodgkin lymphoma.
A previous version of the test examined samples taken from 10,000 women with no prior cancer history. The results, published in April 2020 in the journal Science, showed that the test could more than double the number of cancers found in screening.
“These data demonstrate in a large, well-designed case-control study that combining different cancer biomarkers improves cancer detection, especially in stages I and II, when treatment may be more effective for patients,” said Tom Beer, M.D., Exact Sciences’ chief medical officer and vice president of multi-cancer early detection tests.
There’s still work left to be done for both companies: Exact Sciences is planning to launch a large, prospective, interventional trial of its multi-cancer screening test in 2023, as the company gears up for an FDA submission aimed at getting its test into primary care offices.
Grail, meanwhile, also analyzed the results from the first 38,154 uses of its commercial Galleri test, showing a 1.1% cancer signal detection rate. More than 100 cancers have been confirmed to date by the physicians who ordered the prescription tests, the company said, totaling 28 different cancer types.
Still, it remains to be seen if these positive test results can translate into longer overall lifespans among people diagnosed with cancer.
“This study indicates that hope is on the horizon for detecting cancers that are currently unscreenable, but of course much more work is needed, and with experience and larger samples, these assays will improve,” said Schrag. “It is premature to reach any conclusions about how MCED testing affects mortality, which was not measured in the Pathfinder study and requires lengthy follow-up.”
Other companies making progress in the field include Freenome, which recently launched a large clinical trial of its liquid biopsy, and Guardant Health, which earlier this year at the annual meeting of the American Association for Cancer Research presented data on its multi-cancer screening test, demonstrating high sensitivity in early stage colorectal and lung cancers.
“We need comparative trials across all types of cancer to find out if having an early detection test affects morbidity and mortality,” said ESMO’s André. “We also need to know how the tests benefit patients, and how to discuss the results with them.”
“We need some of these answers before we can calculate the cost impact of introducing MCED tests in routine clinical practice,” he said.