Clinical Trial Data on Use of ctDNA Assays


Experts share their perspective on clinical trial data driving the use of circulating tumor DNA in various settings of cancer care.


John H. Strickler, MD: There have been now, for several years, some interesting studies have published showing the utility of a tumor-informed approach. As you described, the tumor-informed approach involves sending that tumor tissue off and developing a custom or personalized assay. Then you can draw blood after that tumor is removed surgically to assess for the presence of MRD [minimal residual disease] or residual circulating-tumor DNA [ctDNA]. That test has already shown strong prognostic capabilities, meaning where that ctDNA is detected, we see very high rates of recurrence, approaching 100%. Where that ctDNA is negative, we see very low rates of recurrence. Ultimately, to push that needle further, we need to go beyond the prognostic to the predictive, meaning, can I use a positive or a negative result to potentially change what I do for a patient? These studies are ongoing both at the cooperative group level in the United States and then also outside the United States, in Europe, and in Japan. We saw some initial very provocative data presented at ASCO [American Society of Clinical Oncology] this year, and this was also published in the New England Journal, and it’s the so-called DYNAMIC trial [ACTRN12615000381583], based out of Australia. To give you an overview, this took patients with stage II colon cancer who had full resection with no evidence of residual disease. Then they created a tumor-informed assay based on that surgical specimen. Plasma was then collected 4 weeks and then 7 weeks after surgery. If the patient had ctDNA detected, they were obviously high risk for recurrence, so they received adjuvant chemotherapy. If it was negative, then the patient received observation. So, that was one group where you had a ctDNA guided management. Then another group received just standard management, where adjuvant treatment decisions were based on traditional clinical pathologic criteria. What they found is the relapse-free survival was similar for those who received ctDNA guided management versus standard management, but the utilization of chemotherapy went down. It showed that you could potentially use this circulating tumor DNA to reduce overtreatment of patients. It was very interesting data and it suggested there could be a path forward.

Now, out of Japan, we’ve been watching with strong interest the results of the GALAXY study [jRCT1031200006]. This is a just an observational study, but they enrolled 1000 patients over a very short period and looked at outcomes across a broad range of stages. What they found are a few things. Number one, that ctDNA detection, and this is using the tumor-informed approach, at a single postoperative point was associated with a very poor prognosis. A 13-fold higher risk of recurrence if you had DNA detected in blood 4 weeks after surgery. The GALAXY study also found that adjuvant chemotherapy provided very little benefit for patients who are negative at that single postoperative point. Additionally, it found that in those patients who are positive at the single postoperative point, adjuvant chemotherapy improved disease-free survival. So once again, this is an observational study, but it suggests that there could be a role in ctDNA and adjuvant treatment decision. And then finally, the authors in the GALAXY study found that clearance of ctDNA also was associated with improved disease-free survival. That clearance of ctDNA was much more likely with the use of adjuvant chemotherapy. So, a number of interesting provocative findings from the GALAXY study. This further supports the cooperative group studies that are ongoing looking at how we could potentially incorporate this test into our clinic.

Transcript edited for clarity.

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