Issue link: https://viewer.e-digitaledition.com/i/1414760
In a key finding, the modeled positive predictive value (PPV) — the likelihood that an individual with a positive screening test result does indeed have cancer — from the third CCGA substudy (44.4%) tracked closely with the PPV from interim results of PATHFINDER (40.4%), an interventional study of Galleri in a clinical setting involving more than 6,600 patients age 50 and older who had no indications of cancer. Those PPVs are approximately 40 percentage points higher than mammography's, according to Dr. Seiden. Interim results of PATHFINDER were presented at the American Society of Clinical Oncology's Annual Meeting in June 2021, with final results anticipated next year. SEARCHING FOR CANCER SIGNALS To detect and identify the origin of cancer, Galleri relies on a type of genomic signaling called methylation. "Methylation is a biological signal that helps determine tissue and cell type, and which can contribute to cancer development," Dr. Seiden says. "It is a pervasive signal in the genome: There are approximately 30 million CpGs (methyla- tion sites), and [Galleri's] approach leverages approximately 1 million of the most informative methylation sites for cancer signal detection and cancer signal origin prediction. The Galleri … test leverages these signals to detect cancer signal, and when a cancer signal is detected, it predicts where in the body that cancer signal is coming from with high accuracy." Dr. Seiden believes Galleri may allow clinicians to find and start treating aggressive cancers, such as pancreatic and esophageal cancers, earlier, increasing the chance of better outcomes. "Data supports that more aggressive tumor types shed more cell-free DNA into the blood; this makes these cancers inherently more detectable through blood-based testing, even at early stages," he says. "This means that there is significant opportunity for earlier detection of aggressive tumor types that otherwise lack screening tests, and as such have no mechanism for detection when patients are asymptomatic." INVESTIGATIONS CONTINUE CCGA is no longer enrolling patients, but researchers are following participants for five years to better understand their survival and disease status. In June 2021, Galleri became available to individuals in the U.S. with a prescription. It is not intended to replace existing cancer screenings. A large-scale study of U.S. patients who receive Galleri will seek to better understand the test's capabilities vis-à-vis standard screenings and answer lingering questions about the test, such as who is most likely to benefit from it (see "Painting a More Complete Picture of Galleri"). Dr. Seiden and his fellow investigators are excited about the capabilities that Galleri has demonstrated thus far. n Painting a More Complete Picture of Galleri PROVIDENCE, A MULTISTATE health system in the western U.S., will par ticipate in REFLECTION, a study of 35,000 patients undergoing the Galleri multi-cancer early detection blood test. The health system hopes to enroll 5,000 patients divided into a group at high risk for cancer based on risk factors and a primar y care group who may need cancer screenings. Ora Gordon, MD, MS, Clinical Director for the Population Genomics Program at Providence Health, is intrigued by Galleri's potential to identif y many cancers before they are symptomatic and eager to seek answers to several impor tant questions. "Providence … is ver y committed to population health and equity," Dr. Gordon says. "Will a blood test that can screen for multiple cancers at once remove barriers many patients may face in engaging with prevention and screening recommendations? Is there an ideal patient population in terms of age, risk factors and personal histor y, if that makes a difference? Finally, what does a signal positive test with no detectable cancer mean over time?" Dr. Gordon hopes that Galleri may allow oncologists to focus more on preventing than reacting to cancer, as well as remove some of the physical and socioeconomic impediments that prevent many individuals from undergoing standard cancer screenings. 1 5 M D N E W S . C O M /// M D N E W S C E N T R A l P E N N S y lVA N i A ■ 2 0 21