Galleri, a test developed by California-based healthcare company Grail, can detect dozens of types of cancer — most of which currently lack a recommended screening test — with a single blood sample. What could that mean for the way clinicians screen for and treat cancer?
The American Cancer Society projects that 608,570 people will die of cancer in the U.S. in 2021. A key reason for the toll is a dearth of screening tests for all but a handful of cancer types. That leaves many cases of cancer to go undetected until their late, symptomatic stages when the burden of treatment is greater and the risk of mortality higher.
“Current guideline-recommended screening tests in the U.S. save lives, but there are only five that exist, and they screen for a single cancer at a time — colon, cervical, breast, prostate and, in high-risk patients, lung cancer,” says Michael V. Seiden, MD, PhD, President of the US Oncology Network. “The most pressing, unmet need in early cancer detection is thus to identify cancers for which there are no existing recommended screening tests.”
Study results demonstrate Galleri can do just that. In 2020, a substudy of the Circulating Cell-free Genome Atlas (CCGA) study — a case-controlled validation study including more than 15,000 participants with and without cancer — published in Annals of Oncology found that Galleri could identify more than 50 cancer types in all stages with a false-positive rate of 0.7%. The test pinpointed the organ of cancer origin with 93% accuracy. A previous CCGA substudy from 2019 had found that Galleri could detect more than 20 cancer types with a low false-positive rate and precise localization.
In 2021, Annals of Oncology published the results of the third and final CCGA substudy.
“This clinical validation cohort included more than 4,000 participants with and without cancer,” says Dr. Seiden, who is part of the CCGA team. “The specificity was 99.5% (0.5% false-positive rate). The test detected cancer signal from more than 50 types of cancer … and predicted the cancer signal origin in 89% of cases. Being able to identify where in the body the cancer is located with high accuracy is critical to help physicians direct next steps for diagnostic workups.”
In a key finding, the modeled positive predictive value (PPV) — the likelihood that an individual with a positive screening test result does indeed have cancer — from the third CCGA substudy (44.4%) tracked closely with the PPV from interim results of PATHFINDER (40.4%), an interventional study of Galleri in a clinical setting involving more than 6,600 patients age 50 and older who had no indications of cancer. Those PPVs are approximately 40 percentage points higher than mammography’s, according to Dr. Seiden. Interim results of PATHFINDER were presented at the American Society of Clinical Oncology’s Annual Meeting in June 2021, with final results anticipated next year.
Searching for Cancer Signals
To detect and identify the origin of cancer, Galleri relies on a type of genomic signaling called methylation.
“Methylation is a biological signal that helps determine tissue and cell type, and which can contribute to cancer development,” Dr. Seiden says. “It is a pervasive signal in the genome: There are approximately 30 million CpGs (methylation sites), and [Galleri’s] approach leverages approximately 1 million of the most informative methylation sites for cancer signal detection and cancer signal origin prediction. The Galleri … test leverages these signals to detect cancer signal, and when a cancer signal is detected, it predicts where in the body that cancer signal is coming from with high accuracy.”
Dr. Seiden believes Galleri may allow clinicians to find and start treating aggressive cancers, such as pancreatic and esophageal cancers, earlier, increasing the chance of better outcomes.
“Data supports that more aggressive tumor types shed more cell-free DNA into the blood; this makes these cancers inherently more detectable through blood-based testing, even at early stages,” he says. “This means that there is significant opportunity for earlier detection of aggressive tumor types that otherwise lack screening tests, and as such have no mechanism for detection when patients are asymptomatic.”
CCGA is no longer enrolling patients, but researchers are following participants for five years to better understand their survival and disease status. In June 2021, Galleri became available to individuals in the U.S. with a prescription. It is not intended to replace existing cancer screenings.
A large-scale study of U.S. patients who receive Galleri will seek to better understand the test’s capabilities vis-à-vis standard screenings and answer lingering questions about the test, such as who is most likely to benefit from it (see “Painting a More Complete Picture of Galleri”). Dr. Seiden and his fellow investigators are excited about the capabilities that Galleri has demonstrated thus far.