An FDA advisory panel said the benefits of Grail’s multicancer detection test outweigh its risks but acknowledged that there is no proof that the diagnostic can reduce mortality.

In a series of votes, the FDA’s Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee agreed that Grail’s Galleri multicancer early detection (MCED) test was safe (10 yes, 0 no) and effective (6-4), and that the benefits outweighed the risks (7-2, with one abstention).

While the votes on safety, effectiveness, and balance of risks and benefits “relate to the approvability of Galleri,” the committee did not explicitly vote on whether to approve the MCED test.

Galleri has been available as a lab-developed test — at a cost of $949 — by prescription. The test has not yet been approved by the FDA, but Grail submitted an application for FDA approval for use in adults aged 50 years or older.

If the FDA ultimately approves Galleri, the test may be covered by insurance. A law passed in February directs Medicare to cover FDA-approved blood-based MCED diagnostics beginning in 2028. The legislation was supported by several oncology groups, including the American Cancer Society, Pancreatic Cancer Action Network, and Prevent Cancer Foundation.

Some panel members expressed concern that approval could unleash a rush of testing outside of the indicated use, and that although MCED testing might help individual patients, it may not have population-wide benefit.

“There’s going to be people who are going to want to push the system and push the limits beyond the age ranges, and there are going to be doctors, let alone patients, who are going to think that this if this test is negative, I’m good, and they’re not going to get their other cancer screenings,” said panelist Daniel R. Swerdlow, MD, assistant professor of radiology at Georgetown University in Washington, DC.

Swerdlow and other advisers urged the FDA to ensure the label and patient information included language that Galleri should not be used in place of other guideline-recommended cancer screenings, that a positive test might not identify a potential origin, and that someone could test negative but still have a cancer diagnosis.

Galleri analyzes patterns of DNA methylation in fragments of cell-free DNA circulating in the blood to detect a cancer signal. If a signal is detected, Galleri predicts the likely anatomic location of the signal. Galleri cannot detect a signal for all cancers, but Grail says it can flag more than 50.

Effectiveness Debated

Grail submitted data to the FDA from two pivotal studies: PATHFINDER 2 and NHS-Galleri.

NHS-Galleri failed to meet its primary endpoint, and FDA reviewer Catherine Fischer, PhD, MPH, said that the 31.6% sensitivity meant that Galleri did not detect two out of three cancers diagnosed within 12 months following testing. The test had a 66.2% positive predictive value and a 0.26% false positive rate, said Fischer.

The values were similar in PATHFINDER 2, with a 35% sensitivity and a 77% positive predictive value. The false positive rate was 0.15%.

Sensitivity was lower for more common cancer types that have screening protocols, though higher for cancer types that do not have recommended screening, which was encouraging to some panelists.

“What really drove my vote was the ability to screen for cancers that previously are not screenable,” said Danil V. Makarov, MD, MHS, associate professor of urology at NYU Grossman School of Medicine in Brooklyn, New York.

Others said the test was not effective because there was no data on whether testing reduced mortality.

“As an oncologist, I generally look at that as outcomes, and we don’t have that data,” said committee member Stanley Lipkowitz, MD, PhD, deputy director at the National Cancer Institute.

“It has to come back to the outcomes, and I think that we don’t know the answer to that yet,” agreed Victor van Berkel, MD, PhD, a panelist and chief of thoracic surgery at University of Louisville School of Medicine in Louisville, Kentucky.

Jason A. Dominitz, MD, director of the National Colorectal Cancer Screening Program at the VA Puget Sound Health Care System in Seattle, noted that Galleri was clearly increasing cancer diagnoses, but “the clinical benefits are unknown at this time.”

The panel also debated whether the diagnostic findings truly indicated “early detection.”

Charity J. Morgan, PhD, a professor of biostatistics at The University of Alabama at Birmingham, called the notion of early a “very amorphous concept.”

But panelist Kelly Hunt, MD, professor and chair in the Department of Breast Surgical Oncology at The University of Texas MD Anderson Cancer Center in Houston, said detecting cancers that don’t have recommended screening — such as pancreas, esophagus, or bone and soft tissue sarcomas — could be significant.

“If you can detect it earlier, it’s major change in treatment,” Hunt said.

Among the 22 people who spoke during the public hearing were patients who said the test had saved their lives, including an otherwise healthy, asymptomatic firefighter who was diagnosed with a stage I esophageal cancer and is now considered cured.

More Postmarketing Data

Panelists called for more postmarketing data on whether testing has any impact on mortality and more direction on an appropriate testing interval. There was also some interest regarding what happens to people who receive false positive test results.

Grail is conducting several ongoing studies, among them, the REACH trial, which will enroll about 50,000 Medicare beneficiaries who have received usual care plus a Galleri test with a matched comparator arm of beneficiaries receiving usual care alone.

In a statement after the meeting, Grail CEO Josh Ofman, MD, MSHS, said, “today’s vote reinforces the strength of Galleri’s clinical evidence.”

But during the public hearing, Philip E. Castle, MD, MPH, director of the National Cancer Institute Division of Cancer Prevention, urged caution. “The sensitivity for early-stage cancer detection, where intervention matters the most, remains poor,” he said.

“Nobody wants an MCED test on the market more than me, except perhaps those that stand to gain a profit,” Castle said. But “we must not lower the bar for approvals and introduction into the population, regardless of how desperate we are for solutions.”

FDA granted van Berkel a waiver to participate; he is the founder of Breath Diagnostics, a company developing a cancer detection test. Castle and other panelists reported no conflicts.

Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications, including Smithsonian.com. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.