New results for the Galleri blood test, an assay that can detect up to 50 types of cancer, suggest that it could be a useful adjunct to standard screening, say the investigators.
The test has not been approved by the US Food and Drug Administration, but it is available commercially in the United States from Providence Health System for an out-of-pocket cost of around $950. It is being used in England in a pilot trial run by the National Health Service.
The new results are from the Circulating Cell-free Genome Atlas (CCGA) study and were published in Annals of Oncology.
The Galleri test, under development by Grail, uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.
The new results show that specificity for cancer signal detection was 99.5%, so there were few false positive results (0.5%).
However, the overall sensitivity of the test for any stage of cancer was only 51.5%, although it was much higher for cancer of later stages (eg, 90.1% for stage IV cancer).
Cancer signals were detected for more than 50 types of cancer, and overall accuracy of cancer signal origin prediction in true positive results was 88.7%.
“The study is a validation of prior discovery and refinement work on the assay and sets the stage for a new paradigm of screening individuals for multiple cancer with a single blood test, as opposed to the current situation where we screen for individual cancers,” said lead author Eric Klein, MD, chairman of the Glickman Urological and Kidney Institute, Cleveland Clinic, Ohio.
He told Medscape Medical News that the test is intended to supplement, not replace, standard screening tests such as colonoscopy or mammography. “It may be most useful initially in patients at high risk for cancer and is recommended for use in adults with an elevated risk for cancer, such as those aged 50 or older,” Klein said.
However, an expert not involved in the study questioned whether the test is sensitive enough.
Daniel Stover, MD, PhD, medical oncologist with the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, pointed out that there are pros and cons to consider with this test.
“The benefits are that this is a single, minimally invasive blood test for the potential detection of many different types of cancers,” he told Medscape Medical News.
“However, the sensitivity is not perfect ― just over 50% of confirmed cancers were detected via this test, and most of the sensitivity was better among higher-stage cancers,” he noted.
The latest findings are the third and final results from the CCGA study.
The study cohort included 4077 individuals, of whom 2823 had been diagnosed with cancer and 1254 were without cancer. The mean age in the cohort was 60.6 years; among patients with cancer, 54.9% (1552/2823) had stage I/II disease.
Although the overall sensitivity was only 51.5%, the sensitivity of cancer signal detection was much improved with cancer of later stages. The sensitivity was 90.1% with stage IV, 77.0% with stage III, 40.4% with stage II, and 16.8% with stage I cancer.
Sensitivity was also higher in the prespecified group of 12 cancer classes that account for two thirds of cancer deaths in the United States each year (anal, bladder, bowel, esophageal, stomach, head and neck, liver and bile duct, lung, ovarian, and pancreatic cancers, and lymphoma and multiple myeloma). For these cancers, the overall sensitivity was 76.3% for all stages and 67.6% for stages I–III.
To gain further understanding of how the test would perform in a potential screening population, the authors extrapolated the positive predictive value (PPV) and negative predictive value (NPV) as adjusted to SEER cancer incidence and stage distribution among patients aged 50 to 79 years. The PPV for cancer signal detection was 44.4%, and the NPV was 99.4%.
“Planned studies will evaluate its performance and utility in those who have a genetic predisposition to cancer, such as BRCA or Lynch syndrome, and to detect minimal residual disease after treatment for known cancers to monitor for treatment response and as an early indicator of recurrence,” said Klein.
Waiting for Data
Stover also noted that although the test is “exciting in concept, I await more data ― particularly prospective validation and more data within individual cancer types ― before considering its widespread use.
“If validated, this is most likely to be used as a companion test to standard screening approaches, such as colonoscopy and mammography, which are already established screening methods,” said Stover.
He emphasized that there are two major questions concerning the test ― sensitivity and cost. It is unclear whether the test is sufficiently sensitive, and it unknown how it would have a bearing on follow-up studies and the use of biopsy. “Guidance from governing bodies and input from experts in cancer screening and healthcare economics are critical for any new screening test, particularly one that potentially impacts so many patients,” he said.
The study was supported by GRAIL, Inc. Klein is a consultant for Grail.
Ann Oncol. Published online June 25, 2021. Full text
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