ctDNA May Guide Adjuvant Treatment of Colorectal Cancer

Olumide B. Gbolahan, MBBS, MSc

Research has alluded to the prognostic benefit of circulating tumor (ct)DNA-guided adjuvant treatment for colorectal cancer (CRC). However, the question of whether this strategy has enough data to support a shift in practice is unsettled.

According to Olumide B. Gbolahan, MBBS, MSc, ctDNA is helpful when oncologists are deciding whether to give chemotherapy in the adjuvant setting. Also, for patients who experience severe toxicities when being treated in the adjuvant setting, using ctDNA can inform oncologists on whether to proceed with de-escalation or discontinuation of treatment.

In an interview with Targeted Oncology™, Olumide B. Gbolahan, MBBS, MSc, assistant professor, Department of Hematology and Medical Oncology, Emory University, School of Medicine, discussed the evolving role of ctDNA in the adjuvant CRC landscape, and the ongoing research in this space.

TARGETED ONCOLOGY: What is the current role of ctDNA in colorectal cancer treatment?

Gbolahan: In general, ctDNA is useful for patients whom I am sitting on the fence about for whether I want to give adjuvant therapy. It’s also useful for the patients who are sitting on the fence about whether they want to receive adjuvant therapy. I think it's also useful in patients where we have already started adjuvant therapy, and maybe you run into trouble with toxicities, and were trying to make a decision whether we've given enough chemotherapy adjuvantly to stop therapy. It helps with deciding about either stopping therapy or de-escalating therapy.

What research is ongoing that might change the way ctDNA is used in the near future?

The COBRA study [NCT04068103] is a big study that we were all waiting for. It's looking at patients [who] have stage II colon cancer or low-risk disease. It is randomizing patients that may have persistent ctDNA post-surgery to receive adjuvant chemotherapy.

If I find a patient who is low-risk, ctDNA- positive, that normally suggests that maybe they didn't need chemotherapy. We did a study where patients who have low-risk disease and ctDNA-positive blood samples after surgery were randomized to chemotherapy or not. I think that will be important to guide treatment in the future. That is something that I am looking forward to. There's also the ALTAIR study [NCT04457297] that I am looking forward to the results of.

Image Credit: © paolo toscani [stock.adobe.com]

What biomarkers should oncologists look for in the ctDNA of patients with CRC?

The biomarkers will fall into 2 broad categories; the biomarkers that would predict response to treatment, whatever treatment we offer patients, and then biomarkers that may help us with prognostication. I think that the ctDNA assays are adding information to prognostication. They will be helpful to determine how patients respond to therapy.

I think it's important that as a biomarker for prognosis, everybody should be tested for mismatch repair protein status on their tumors. I think that this is important for not just prognosis, yes, it's useful for making decisions about genetic counseling, but depending on the stage of the disease, for instance, for stage IV cancers and more advanced cancers, even for colorectal cancer that’s resectable, this is also useful for picking treatment options in terms of chemotherapy vs immunotherapy. Mismatch repair protein status is a useful marker in colorectal cancer.

There are other genomic tests that we do that may be helpful that are helpful for prognosis and prediction of response to treatment like BRAF mutation status, KRAS mutation status, HER2 status, and things like that. There are a bunch that are already available and ctDNA will just add to that information.

Can you talk about the DYNAMIC study? What did oncologists learn from it?

The DYNAMIC study [ACTRN12615000381583] was published in the New England Journal of Medicine earlier this year. The highlight of the study is that patients who had stage II colon cancer were randomized to 2 groups. One group was treated per the standard-of-care. So, we identified the usual risk markers, and based on the risk markers, patients are offered adjuvant therapy or not. The other group of patients were treated based on the presence of ctDNA.

I think the highlight of that study was that those who were randomized to ctDNA-guided management, physicians who were treating based on that information tended to use less chemotherapy overall than those who were being treated were treating per standard management. About 28% of patients received standard management chemotherapy for their colon cancer adjuvantly whereas those who were who are using ctDNA assay to guide their money management, only about half of the that percentage received adjuvant chemotherapy.

Do you think the field has reached the point during which ctDNA can guide adjuvant therapy in CRC?

I don't think it's time. I think that the data are still coming. I think we should wait for the data to mature for us to widely accept this. I also think that on a case-by-case basis, the science is compelling enough that we can pick patients who we can use it for decision making. But for the community oncologists who are treating colorectal cancer, I think that there's still there's still data to read out. That would help us. The DYNAMIC study showed us very compelling data, but I’m not sure that’s the final word.