Grail LLC, and the University of Oxford announced results from the prospective Symplify study which was presented during an oral session on Saturday (June 3) at ASCO 2023 (the American Society of Clinical Oncology) annual meeting in Chicago.
The study is the first large-scale evaluation of an MCED test in individuals who presented to primary care and were referred for diagnostic follow-up for suspicion of cancer. The analysis showed strong performance of Grail’s MCED methylation-based platform in the symptomatic population of more than 6,000 patients and demonstrated the feasibility of using an MCED test to assist clinicians with decisions around the route of referral from primary care. These results are in press for publication in The Lancet Oncology.
Brian Nicholson is associate professor at the Nuffield department of primary care health sciences, University of Oxford, UK, and co-lead investigator of the study.
He said: “Earlier cancer detection and subsequent intervention has the potential to greatly improve patient outcomes. Most patients diagnosed with cancer first see a primary care physician for the investigation of symptoms suggestive of cancer, like weight loss, anemia, or abdominal pain, which can be complex as there are multiple potential causes.
“New tools that can both expedite cancer diagnosis and potentially avoid invasive and costly investigations are needed to more accurately triage patients who present with non-specific cancer symptoms.
“The high overall specificity, positive predictive value, and accuracy of the cancer signal detected and cancer signal origin prediction that was reported across cancer types in the SYMPLIFY study indicate that a positive MCED test could be used to confirm that symptomatic patients should be evaluated for cancer before pursuing other diagnoses.”
The Symplify study enrolled 6,238 patients, aged 18 and older, in England and Wales who were referred for urgent imaging, endoscopy or other diagnostic modalities to investigate symptoms suspicious for possible gynecological, lung, lower gastrointestinal (GI) or upper GI cancer or who had presented with non-specific symptoms.
Participants provided a blood sample, from which cell-free DNA was isolated and stored until Grail’s MCED test was performed in batches, blinded to clinical outcome.
If a cancer signal and therefore origin was detected through the test’s predictions, these were compared with the diagnosis obtained by standard care to assess the test’s performance.
Symptoms that were reported more commonly leading to referral included unexpected weight loss (21.4%), change in bowel habit (22%), post-menopausal bleeding (16%) rectal bleeding (15.7%), abdominal pain (14.5%), pain (10.6%), difficulty swallowing (8.8%) and anemia (7.1%).
Within the study, 368 (6.7%) of the 5,461 evaluable patients were diagnosed with cancer through standard of care. The most common cancer diagnoses were colorectal (37.2%), lung (22%), uterine (8.2%), esophago-gastric (6%) and ovarian (3.8%).
GRAIL’s MCED test detected a cancer signal in 323 people, 244 in whom cancer was diagnosed, resulting in a positive predictive value (PPV) of 75.5%, negative predictive value (NPV) of 97.6%, and specificity of 98.4%.
The overall sensitivity of the MCED test was 66.3%, ranging from 24.2% in stage 1 cancers to 95.3% in stage 4, and increased with age and later cancer stage. The overall accuracy of the top CSO prediction after a positive MCED test was 85.2%. The mean age of patients in the study was 62.1 years old.
Sir Harpal Kumar, president of Grail Europe, said: “Grail’s earlier Pathfinder study previously demonstrated that adding Grail’s MCED testing to standard of care screening more than doubled the number of cancers detected compared with standard screening alone in adults with no symptoms or suspicion of cancer.
“Now, the Symplify data confirm the potential benefit of methylation-based MCED blood tests as a diagnostic aid for use in the symptomatic patient population.
“These exciting results will inform our development of an optimized classifier for use in symptomatic patients with a suspicion of cancer.”
The University of Oxford sponsored the Symplify study and was responsible for data collection, analysis and interpretation. The study was funded by Grail with support from National Health Service (NHS) England, NHS Wales, the National Institute for Health, and Care Research (NIHR) and NIHR Oxford Biomedical Research Centre.
Helen McShane, director of the NIHR Oxford Biomedical Research Centre, said: “This is a fantastic example of how academia and industry can work together for patient benefit, recruiting over 6,000 patients to Symplify in under six months and within less than a year of launching the project.
“We are committed to diagnosing cancers earlier, when they can be cured, and this study is an important step on that journey. Symplify also shows that we can run trials at scale using digital systems to deliver research quickly and cost effectively, with the help of the NIHR’s Clinical Research Network.”