Dr Whitney Jones Discusses Multi-Cancer Early Detection Testing

Whitney Jones, MD, chief medical advisor at GRAIL Inc, discusses the implications of results from the PATHFINDER study (NCT04241796) on multi-cancer early detection (MCED) testing.

How can the results of the PATHFINDER study impact future research on MCED tests?

The PATHFINDER [trial] was our first return-of-results study, so it's really critical. About 6500 people, all very well screened, had this test done “in the wild”—so doctors got the results and decided how to work those patients up and how to evaluate them. And the critical take-home messages for this [included] the performance of the test, [which] was essentially identical to what we had demonstrated in our case-control trials that led to the formulation of the tests, and those were the CCGA [Circulating Cell-free Genome Atlas] trials. So the take-home message is, number 1, that performance is the same. The specificity remained very high, the positive predictive value remained very high—about 43%. In addition, about 70% of the cancers that we diagnosed had no screening outside of USPSTF guidelines. So again, that capacity for multi-cancer [early detection tests] to broaden the number of cancers screened beyond the 30% that we [currently] screen, in fact screening 100%, [is significant]. Number 2: Almost 50% of the cancers that we diagnosed were in stage I and stage II. Knowing that stage shift is a marker for the ability to have better outcomes with treatment was a really huge impact for that. The third piece was that we [more than] doubled the number of cancers detected by routine USPSTF screenings with the multi-cancer early detection tests. That's impacting dramatically the cancer detection rate, which is really our focus and goal: to increase the number of cancers we're finding as pre-symptomatic, earlier stage cancers, so we can have more effective treatment. Cancer is more treatable the earlier it's detected.

Do the results have enough support to impact clinical decisions? How so, or what next steps are needed to get there?

At GRAIL, we've developed an extremely robust basis, based on our scientific studies, for implementing this. That was really the impetus—we wanted to bring this amazing technology to market so we could start saving lives now. Again, even though there were only 6500 people in that study, it was shown to be safe. We essentially mirrored our performance. I think that, along with the additional studies that we've brought—the CCGA studies, and we’re involved in a huge trial with the National Health Service with over 140,000 individuals randomized into two arms. We think the data is robust and supports utilizing this in the screening environment for people who are at elevated risk of cancer, such as those aged 50 and over. We absolutely think that the test itself was robust and helped us lead into the space and really proved the concept that we had developed in our case-controlled clinical trials.