September 24, 2026
9 min read
Key takeaways:
- The panel voted 7 to 2 with one abstention that the benefits of Galleri outweigh potential risks for multicancer detection.
- Clinical efficacy remains uncertain with long-term outcome data still needed.
An FDA advisory panel expressed support for a blood test designed to detect early signs of multiple cancers, including some for which no screening alternative exists.
Members of the Medical Devices Advisory Committee’s Molecular and Clinical Genetics Panel voted 7 to 2 with one abstention that the benefits of Galleri (Grail Inc.) outweigh the potential risks for adults age 50 years or older, the population for which the test’s developer is seeking approval in the United States.
An FDA advisory panel expressed support for a blood test designed to detect early signs of multiple cancers.
In separate votes, the panel unanimously agreed Galleri is safe for use in this population but was split on whether the test is effective. On the latter question, six members voted yes and four voted no.
The FDA is not obligated to follow advisory committee recommendations when making decisions about approval but often does so.
“What drove my vote was the ability to screen for cancers that previously have not been ‘screenable.’ I think that would be a major contribution,” said panel member Danil V. Makarov, MD, a board-certified urologist at NYU Langone Health who endorsed the test’s benefit-risk ratio.
However, several panel members — even some who cast favorable votes — expressed caution, citing a lack of long-term data to show whether the test’s identification of cancer signals translates to improved clinical outcomes.
If the test ultimately is approved, Makarov said he hopes “robust post-market surveillance” will be conducted.
Victor van Berkel, MD, PhD, thoracic surgeon and associate professor in the department of cardiovascular and thoracic surgery at University of Louisville School of Medicine — said he considered abstaining before ultimately casting a favorable vote.
“I suppose the reason I hedge toward ‘yes’ is because I think, in the years ahead, it probably will be proven to have benefits that outweigh the risks, specifically when it comes to cancers for which we don’t have good tests,” van Berkel said. “I think even a marginally successful test, if we can find more early-stage cancers that we can’t screen for currently, will end up having benefit. But I don’t know if that has been proven yet. Perhaps my ‘yes’ is a hopeful rather than an accurate one.”
‘Not a replacement’
Only about one in seven cancers in the United States are detected through guideline-recommended screening, according to data from NORC at University of Chicago.
Malignancies for which no screening test exists account for approximately 70% of cancer deaths.
Multicancer early detection (MCED) tests that measure biologic signals in blood, urine or other body fluids have been touted as one potential strategy to improve detection of those cancers and possibly identify them prior to metastatic spread.
Galleri — available only with a physician prescription — is a next-generation sequencing-based in vitro diagnostic test intended to detect cancer-specific methylation patterns in cell-free DNA. Because it is investigational, most people who use the test pay out-of-pocket.
A premarket approval application for Galleri is the first submitted to the FDA for an MCED, and approval likely would prompt insurance companies to cover the test.
The Medical Devices Advisory Committee’s Molecular and Clinical Genetics Panel dedicated a day-long meeting Sept. 23 to the application.
Nearly two dozen physicians and advocates — as well as members of the public who shared stories about how the test detected signals that led to diagnosis of early-stage cancers while they were asymptomatic and otherwise healthy — spoke during the session.
The session also included review and discussion of data from two large studies that evaluated the performance of Galleri.
The NHS-Galleri trial — the first randomized trial to evaluate whether an MCED test using a blood sample could result in diagnosis of cancer at earlier stages — included adults in the U.K. aged 50 to 77 years with no clinical suspicion of cancer.
Researchers evaluated whether the addition of 3 years of annual testing with Galleri to standard screening could result in detection of 12 prespecified cancers at earlier stages — specifically increasing the proportion diagnosed at stage I or stage II while decreasing the number diagnosed at stage III or stage IV. The cancer types evaluated included bladder, esophageal, head and neck, ovarian, pancreatic and stomach cancers.
As Healio previously reported, findings presented at last year’s ASCO Annual Meeting and later published in The New England Journal of Medicine showed NHS-Galleri did not meet its primary endpoint, failing to show a reduction in stage III/stage IV diagnoses of the prespecified cancer types after three annual screening rounds (HR = 1.03; 95% CI, 0.92-1.14).
Analyses of secondary endpoints showed a reduction in stage IV cancers alone, as well as a 16% increase in detection of stage I/stage II cancers among trial participants who underwent annual screening with Galleri for 3 years compared with those who received usual care (HR = 1.16; 95% CI, 1.03-1.3).
The test exhibited a specificity of 99.55% and a positive predictive value of 52%.
Galleri has been designed to predict the site in which a cancer signal originated. When the test reported one site of origin, it proved correct in 87% of cases. When the test reported the top two most probable sites of origin, it proved correct in 92.5% of cases.
A second prospective study — PATHFINDER 2 — evaluated the safety and performance of Galleri in combination with standard cancer screenings in the U.S. and Canada. The study included nearly 36,000 adults aged 50 years or older with no clinical suspicion of cancer.
Findings published this week in Nature Medicine showed adding Galleri to clinically recommended screening for breast, cervical, colorectal and lung cancers resulted in a 6.5-fold increase in the number of detected cancers, about 70% of which were malignancies for which no national screening recommendations exist.
Nearly half of cancers diagnosed were stage I or stage II.
“[The test] finds many of these cancers while they’re still asymptomatic and localized, when cure is still possible,” Nima Nabavizadeh, MD, lead author of PATHFINDER 2 and director of early detection clinical research at Oregon Health & Science University Knight Cancer Institute, said in a press release. “It’s not a replacement for standard screening, but a powerful complement to it. Used together, we catch far more cancers early.”
In PATHFINDER 2, Galleri demonstrated a positive predictive value of 60.3% and achieved 99.64% specificity, equating to what Nabavizadeh described as an “extraordinarily low false-positive rate” of 0.36%.
‘A little bit premature’
Although MCED tests are intended to detect signals of cancer at early stages, multiple advisory panel members expressed concern about use of the word “early” in a potential product label, noting the test’s effectiveness for “early detection” had not been clearly established.
Several panel members indicated they were reassured by the low rate of false-positive results, as well as the low number of individuals who received false-positive tests who subsequently underwent invasive procedures.
However, they expressed concerns about indirect risks of the test.
These included the possibility that patients may use the blood test instead of — not as a complement to — other available routine cancer screenings, as well as the risk that people may interpret a negative test to mean they definitively do not have cancer, prompting them to ignore symptoms or other screening recommendations.
“False reassurance is the largest issue,” van Berkel said. “I struggle a little bit with what to do when it is obvious that the target audience will misinterpret the results. … There were a couple physicians in the public comments who said something along the lines of ‘This test not only finds cancer, but it rules it out,’ which this test clearly does not do. … It’s not just patients who are going to misinterpret this, but physicians.”
Panel member Daniel Swerdlow, MD, assistant professor in the department of radiology at Georgetown University, agreed that “robust education” will be needed for health care professionals who order the test “so they really understand what it means.”
Swerdlow also expressed concern about downstream effects of positive results from Galleri or other MCED tests.
“A lot of them [relate to] solid organ tumors, which will require imaging to confirm, and many of the rest will require endoscopy,” he said. “We already don’t have enough trained endoscopists to do the routine screening colonoscopies needed in this country. By the same token, there is a massive shortage of radiologists in this country. … It’s not the imaging test that produces the finding, it is the radiologist who is interpreting the test. There are not enough of us, and it’s not going to change any time soon.”
Aditya K. Ghosh, MD, senior associate consultant in the division of general internal medicine at Mayo Clinic in Minnesota, countered that — in his experience — less than 1% of people who take MCED tests have positive results. The ability for MCED tests to help pinpoint a potential source of origin for a cancer signal also has been “extraordinarily helpful” for guiding patient workup and should be “an important piece” in determining a test’s effectiveness, Ghosh added.
For other panel members, though, questions about the test’s ultimate impact on outcomes represented the greatest reason for pause.
Although van Berkel voted that the test’s benefits outweigh the risks, he was among the four panel members who indicated in a separate voting question that the test’s effectiveness for the intended publication had not been established.
The members of the public who spoke about being diagnosed with cancer following a Galleri test result “were obviously incredibly passionate, and rightfully so,” van Berkel said.
“The problem is, we can’t look at it just from the point of view of that one person,” van Berkel continued. “We have to look at it from the point of view of the entirety of society. As a clinician, finding an early-stage cancer that could save somebody’s life is incredibly important. But from a scientific standpoint, it has to come back to outcomes. I don’t think we know the answer to that yet. I do think the data are coming, but this feels like we’re a little bit premature.”
Stanley Lipkowitz, MD, PhD, chief of NCI’s Women’s Malignancies Branch and the lone advisory panel member to abstain from voting on whether Galleri’s benefits outweighed the risks, shared a similar sentiment.
“The question comes down to what you call clinical effectiveness,” Lipkowitz said. “Many of us will look at it in different ways but, as an oncologist, I generally look at that as outcomes. I honestly feel we didn’t have the data to show this is clinically effective. … If we approve [Galleri] without that, all of the subsequent tests won’t need that, either. I think we need to set the bar higher because this is the first one. It is a transformative test, but that unfortunately means we really need to be more critical before we approve it.”
‘An encouraging milestone’
The FDA advisory panel’s vote represents “an important and encouraging milestone for multicancer early detection,” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and coleader of the kidney cancer program at Dana-Farber/Harvard Cancer Center, told Healio.
Toni K. Choueiri
“The major potential impact is the ability to detect multiple cancers, including many for which we currently have no effective population screening test, from a single blood draw,” Choueiri said.
However, Choueiri acknowledged he shares concerns about the lack of long-term data showing whether the test improves clinical outcomes.
“The NHS-Galleri randomized trial did not significantly reduce the primary endpoint of stage III/IV cancers, although there was a potentially encouraging reduction in stage IV disease, so longer follow-up — and, if approved, rigorous post-market surveillance — will be essential to determine whether earlier detection ultimately translates into fewer advanced cancers and improved survival,” Choueiri said.
He also emphasized Galleri should complement, not replace, established screening, and that clinicians must “remain attentive” to false-positive and false-negative results.
“It will be interesting to see what the national guidelines will be if the FDA ultimately approves this test,” Choueiri said, noting he also would be curious to see the positions of entities such as ASCO, American Association for Cancer Research, American Cancer Society, National Comprehensive Cancer Network and the U.S. Preventive Services Task Force.
“Of course, it will be also as interesting to see the coverage by Medicare or insurance carriers for that test,” he added.
For more information:
Toni K. Choueiri, MD, can be reached at toni_choueiri@dfci.harvard.edu.
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