Tanios S. Bekaii-Saab, MD, on Using Assays to Predict Outcomes and Select Adjuvant Therapy in Stage II CRC

When asked by CancerNetwork^® about the most important data to come out of the 2022 American Society of Clinical Oncology Annual Meeting, Tanios S. Bekaii-Saab, MD, Gastrointestinal Cancer Program lead at the Mayo Clinic Cancer Center and medical director of the Cancer Clinical Research Office as well as vice chair and section chief for Medical Oncology in the Department of Internal Medicine at the Mayo Clinic in Phoenix, Arizona, talked about data from the phase 2 DYANMIC trial (ACTRN12615000381583) examining circulating tumor DNA–guided approach to adjuvant therapy selection in colorectal cancer.

Transcript:

The other study of interest at ASCO was called DYNAMIC that essentially looked at circulating tumor DNA and its value as a tumor-informed platform. That would be the Signatera platform and other similar platforms. You have to have the tumor and match [what’s in the] blood to the tumor. This was for stage II colon cancers across the board, both low risk and high risk were included. The aim was primarily randomizing patients 2:1 to testing vs no testing. For those who are tested, the results [inform treatment selection. With a positive result], you give chemotherapy, but with negative, you do not give chemotherapy standard of care. [The aim of the study was to show] you don’t lose benefit by a noninferiority design, with relapse-free survival [RFS] at 2 years as the primary end point. Another relevant end point was adjuvant chemotherapy use in each arm.

What they found is that the [RFS] at 2 years was noninferior, meaning that there was no loss of benefit when you test vs not. The second relevant finding was that the utilization of adjuvant chemotherapy almost dropped by half when you test and act on the test. This sounds great, and that certainly tells the story more and more for us about the utility of this test. The problem today—I'll be very frank, and I think a lot of my colleagues agree with this—is that if I have a patient with high-risk stage II colon cancer and I have a test that’s negative, am I going to withhold chemotherapy from that patient? The answer is clearly no at this point. The question of benefit vs no benefit from chemotherapy in the presence of a negative test has not been addressed. This being addressed in prospective trials, but today in clinic, I cannot with all due consciousness withhold chemotherapy from a patient who has high risk of relapse, regardless of what the Signatera or any other platform tells me.

On the other hand, if it’s positive, am I going to expose a patient to fluoropyrimidine plus or minus oxaliplatin based on the results of the test. The answer is, again, tricky. Common sense says I have to treat them if it’s positive. But then one takes a step back and says when it’s positive, it’s likely to indicate an increased chance of recurrence. But so far, what we know about chemotherapy in this setting is that it may delay recurrence rather than add to the cure, for now at least. There are hints that chemotherapy may add to the cure for some of these patients, but we don’t have that signal yet. Overall, it’s a study that’s going in the right direction, but I don’t think it has given us a final answer. We are awaiting the results of CIRCULATE-Japan, CIRCULATE-US [NCT05174169], and more are going to give us better perspective and understanding of the predictive value of these tests.

Reference

Tie J, Cohen J, Lahouel K, et al. Adjuvant chemotherapy guided by circulating tumor DNA analysis in stage II colon cancer: the randomized DYNAMIC trial. J Clin Oncol. 2022;40(suppl 17):LBA100. doi:10.1200/JCO.2022.40.17_suppl.LBA100