Latest Insights from the PATHFINDER Study: Cancer Detection Advancements

Transcript:

Jon O. Ebbert, MD: There was another seminal study called the PATHFINDER study [NCT04241796], and lots of exciting results coming out about that recently. Maybe, if you could for us, describe the key objectives in overall study design and maybe feather and some comments about how the PATHFINDER study is different from previous studies.

Tom Beer, MD, FACP: Sure. Thank you for that question. So the PATHFINDER study is a little bit more recent than the DETECT-A study. It has been presented. We’re still awaiting the publication of the final results of that study. It examined the Galleri test, the methylation-based test and development by Grail. It was a prospective interventional study, and the primary objective was really to study the implementation of the test in that population, to examine how clinicians would approach the diagnostic evaluation of patients with MCED [multicancer early-detection] test. There are a whole host of secondary objectives to the study, including examination of test performance. Another objective of that study included assessment of anxiety and distress associated with MCED testing. And that’s an important topic for studies to consider as we look at this new technology.

The study enrolled 6621 and analyzable participants. They were all over the age of 50, and 2940 were of average cancer risk, and 3681 had an elevated risk of cancer. And that included individuals who are smokers, who had a genetic predisposition to cancer, and who actually had a prior history of cancer. So it was a higher-risk group. About 1.5% of all participants had a positive MCED test result. So a little bit higher than in DETECT-A, probably reflecting the somewhat higher-risk group that was enrolled here. Blood was drawn for an MCED test and returned to the provider, the patient, and in this study, the provider determined how to best evaluate a positive signal. And the test provided information about a suspected organ of origin, so-called TOO, or tissue of origin, or CSO, cancer signal of origin, information that clinicians could use to decide on the direction of the work-up. Cancer status was assessed at the end of 12 months, and that provided for the primary results of the study.

Jon O. Ebbert, MD: Certainly a lot of rich data coming out of that study. Maybe there’s an opportunity for you to kind of walk through some of the main findings of that study that we can take home.

Tom Beer, MD, FACP: Sure. So there were 92 participants who had a positive cancer signal on an MCED said. There were 35 cancers diagnosed as a consequence of the MCED test. The median time to diagnostic resolution was about 79 days, 57 days for [participants] with a true positive result, and 162 days for those with a false-positive result. I would caution, though, that these are research numbers from investigators who were using an MCED for the first time in a research setting. The study was also conducted during the COVID[-19] pandemic. So much like DETECT-A, I don’t know that the time to diagnostic resolution is really indicative of what to expect as the tests become more routine. Most participants required some form of imaging, not surprisingly, for diagnostic resolution, about 92%, and 89% received some form of advanced imaging.

In those individuals with a true positive result, in other words in those individuals who turned out to have a cancer, the accuracy of the organ of origin prediction was 85% for the first organ of origin suggested, and in some cases the test offered first and second choices, and between the first and the second choices put together, the accuracy was 97% in true positive patients. There were 121 total cancers diagnosed in the 12-month period in these 6000 patients, so close to a 2% rate of cancer diagnoses, again reflecting the relatively higher-risk cohort that was studied here. So 35 of those were diagnosed as a result of the MCED, 29 were diagnosed as a consequence of standard-of-care screening, 9 were diagnosed as a result of screening that is not considered standard of care. And then the remaining cancers, as one would expect, were a result of a clinical diagnosis.

The majority of cancers were diagnosed in a high-risk cohort, and there was an almost even split between solid tumors and hematologic malignancies. There were 18 participants with 19 solid tumors and 17 participants with 17 hematologic malignancies. The primary results reported in PATHFINDER involved a prototype version of the Galleri test, and that that version had a reported sensitivity of 29% at a specificity of 99.1% and a positive predictive value of 38%. The samples from PATHFINDER were also used to examine an updated version of the Galleri test that reflects the test that is currently available as a laboratory-developed test, and their sensitivity was 21% at a specificity of 99.5% and a positive predictive value of 43%.

Transcript is AI generated and edited for readability.