GRAIL, a healthcare company for early cancer detection, announced detailed findings from the PATHFINDER study of its multi-cancer early detection (MCED) blood test have been published in The Lancet.
The study, conducted in 6,662 adults over the age of 50 without symptoms suggestive of cancer, demonstrated that an earlier version of GRAIL’s MCED test identified many cancer types that do not currently have recommended screening tests, enabled targeted cancer diagnostic evaluations, and supported diagnostic resolution for the majority of participants in less than three months.
“The possibility of screening for multiple types of cancer simultaneously using a blood specimen is promising both because there are no effective screening strategies for many types of cancer and because strategies with established effectiveness require considerable time and effort,” says Deb Schrag, MD, MPH, chair, department of medicine at Memorial Sloan Kettering in New York and a PATHFINDER investigator. “The PATHFINDER study was a pilot non-randomized study to evaluate how patients and clinicians would respond to a blood test to screen for multiple cancer types. The screening test identified a cancer signal in 1.4% of participants, 0.5% of whom were confirmed to have cancer. In the vast majority of cases, the test accurately predicted the type of cancer. This study demonstrates the feasibility of screening for multiple cancers using a blood test and lays the foundation for large, controlled trials necessary to establish clinical utility and cost-effectiveness.”
The prospective cohort assessed use of GRAIL’s targeted methylation-based MCED test with 6,662 enrolled participants in U.S. outpatient settings to determine the time required and diagnostic testing necessary to reach a diagnostic resolution following a cancer signal detected test result (primary endpoint). Study results showed that the GRAIL test cancer signal origin (CSO) prediction was 97% accurate and directed the clinical workup, leading to resolution of the cancer diagnosis in less than three months (median 79 days) among participants who received a cancer signal detected result.
In the study, when added to U.S. Preventive Services Task Force (USPSTF) standard of care screening, GRAIL’s MCED test more than doubled the number of cancers detected compared to standard screening alone, according to the company. Of those who received a cancer signal detected result, 36 cancers were diagnosed in 35 participants (one participant was diagnosed with two cancers). Standard screenings identified 29 cancers.
“The PATHFINDER study provides crucial insights into how MCED testing can be used in clinical settings and demonstrates its additive benefit for cancer screening in clinical practice for eligible patients,” says Jeffrey Venstrom, MD, chief medical officer at GRAIL. “MCED tests have the potential to expand the number of cancers detected with a low false-positive rate when added to recommended single-cancer screenings. In addition, our MCED test can predict the cancer signal of origin, resulting in a more efficient and targeted diagnostic evaluation to help decrease unnecessary tests, radiation and costs. We believe this study helps pave the way for its clinical adoption, with the aim of reducing the burden of late-stage cancer.”
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Among participants who received an MCED cancer signal detected result and had a confirmed new cancer diagnosis (true positives), nearly half (48%) were detected at an early stage (I-II) when the potential for curative treatment is increased. Importantly, 74% of the MCED-detected cancers were cancer types that do not currently have recommended screening tests. These included cancers of the bile duct, small intestine, pancreas and spindle cell neoplasm, all highly lethal cancers that may be amenable to surgical resection at early stages.
“The PATHFINDER trial gave us a glimpse into the future of cancer, early detection and cancer screening and showed us how a multi-cancer early detection blood test can have tremendous potential to impact patient outcomes,” says Charles McDonnell, MD, radiologist at Sutter Medical Group and PATHFINDER investigator. “The more broadly that we can get the message out about multi-cancer early detection technology, the more people can continue to study and incorporate this into clinical practice, the better for our patients.”
After the PATHFINDER study was launched, a refined version of the MCED test, now available by prescription as Galleri, was developed for clinical use. The refined test only changed the threshold for detecting a cancer signal for hematologic malignancies, removed indeterminate as a returned cancer signal origin result and limited the number of CSOs. The study assessed performance of both the early version and the refined version as a key secondary endpoint. Results showed the positive predictive value (PPV, the percent of cancer signal detected results that were confirmed to be cancer) of the refined test was 43.1% compared to 38% with the earlier version. The refined test version also improved specificity, or the percentage of true negatives, to 99.5%, increasing from 99.1% with the earlier version. The CSO prediction accuracy of the refined test was 88%.
No study-related serious adverse events were reported as a result of MCED testing in the study, and there were no adverse events reported from diagnostic workups.
