Trial fails to meet primary goal
A blood test for more than 50 types of cancer that was once hailed as the holy grail of oncology has failed its primary objective in a landmark UK trial involving 142,000 NHS patients, data presented at the world’s largest cancer conference have revealed.
The NHS-Galleri trial, which enrolled 142,942 people aged 50 to 77 with no cancer symptoms, aimed to assess whether adding the multi-cancer early detection (MCED) test to standard screening could shift diagnoses to earlier, more treatable stages. Every participant had blood drawn once a year for three years and received the recommended cancer screening tests. Half of the samples were analysed using the Galleri test; the other half served as a control group. Those who received a positive Galleri result underwent diagnostic follow-up, as did anyone in either group who developed symptoms.
The trial’s primary endpoint was a combined measure of stage three and stage four diagnoses in a pre-specified group of 12 cancers. Results showed no statistically significant reduction in advanced cancers between the Galleri group and the control group — meaning the test did not achieve its main goal. Dr Julie Gralow, chief medical officer and executive vice-president of the American Society of Clinical Oncology (Asco), which hosted the meeting in Chicago, said: “While the Galleri-NHS study results show some encouraging trends toward tumour downstaging, it is important to recognise that the trial did not statistically reduce late-stage cancers by its predefined primary endpoint.” One senior cancer figure who spoke on condition of anonymity was more blunt: “The trial flopped. Clear and simple.”
Encouraging secondary findings
Despite the headline failure, Grail, the California-based company behind Galleri, pointed to several secondary results it described as clinically meaningful. Researchers highlighted a 14% reduction in stage four cancers overall after the three screening rounds, with decreases of 22% and 26% observed in the second and third rounds respectively for the pre-specified group of 12 deadly cancers. The addition of Galleri also led to a 16% increase in the diagnosis of stage one and two cancers for those same cancer types, and the overall cancer detection rate rose four-fold compared with standard screening alone. The study further indicated a 21% decrease in cancers detected after symptomatic presentation and a 25% reduction in cancers diagnosed through emergency presentation.
Grail’s chief scientific officer, Harpal Kumar — a former chief executive of Cancer Research UK — said: “Galleri represents a potential transformational shift in cancer detection.” The test’s performance metrics, drawn from other studies, showed high specificity, with a false positive rate of between 0.4% and 0.55%, and a positive predictive value of 52% to 62%, meaning over half of positive results led to a cancer diagnosis. Its ability to predict the origin of a cancer signal was accurate in 90% to 93.4% of cases. Overall sensitivity for all cancer types across all stages was 51.5%, rising to 76.3% for the 12 deadliest cancers. The SYMPLIFY study, conducted in people with symptoms that might have been cancer, found that 76% of positive Galleri tests led to a diagnosis, while PATHFINDER 2 in the US showed a seven-fold increase in detection when added to standard screenings.
Expert scepticism
Independent experts urged caution. Professor Richard Houlston, head of the division of genetics and epidemiology at the Institute of Cancer Research, London (ICR), said the researchers had presented their findings “far more positively than the overall results justify”. He emphasised: “The study’s main goal was to show a reduction in late-stage cancers overall, and this primary endpoint was not met. While some secondary findings are encouraging, in so far as a possible reduction in the most advanced cancers after repeated screening rounds, these results remain uncertain and should be interpreted cautiously.” He added: “The failure to meet the primary endpoint is the crux of the issue here. Mortality outcomes will be available in a couple of years, examination of which will be warranted. However, on the basis of results from this and smaller trials, there is no evidence base upon which to justify implementation of Galleri at a population scale.”
Cancer Research UK said it did not yet know whether the test could reduce cancer deaths in people without symptoms and would need to analyse the data further to assess its potential use in the NHS. The organisation also highlighted the need to support a wide range of multi-cancer tests with early detection potential. Asco’s updated guideline on liquid biopsies will support their use in monitoring and defining diagnosed cancers but will not yet recommend them for early cancer detection. Some experts raised concerns about the test’s cost — out-of-pocket expenses exceeding $1,000 — and the strain it could place on NHS diagnostic capacity if it diverted resources from symptomatic patients. Professor Peter Johnson, the national clinical director for cancer at NHS England, said: “We look forward to seeing the data from the trial in detail, to help us make decisions on what this could mean for the NHS in the future.”