CRC: Clinical Trial Landscape for MRD-Based Early Intervention


An overview colorectal cancer clinical trials studying early intervention based on MRD positivity.


Tanios S. Bekaii-Saab, MD: I’m glad you brought in the perspective of trials that are ongoing. I’ll let you continue you by telling us a little more about the landscape of the clinical trials, specifically those that are geared toward early intervention based on MRD [minimal residual disease] assessment. That includes your trial and the differences between the 2 studies: CIRCULATE-US and 1 of the arms and then your study. Talk a little about that.

Aparna Parikh, MD, MS: There are many trials across the globe thinking about how to integrate these tests into care. One of the largest US trials is CIRCULATE-US, which is looking at stage III patients and high-risk stage II patients and determining whether chemotherapy is needed based on MRD [minimal residual disease] testing. CIRCULATE-US also follows patients over time serially. If you’re initially negative, then you could get randomized to no therapy. But if you turn positive over time, you have the option of going on to an escalation of care. There are many arms, including escalation to things like FOLFIRINOX [5-fluorouracil, leucovorin, oxaliplatin, irinotecan], for positive patients vs standard-of-care FOLFOX [5-fluorouracil, leucovorin, oxaliplatin] for higher-risk patients.

Our study isn’t looking at the time of initial adjuvant chemotherapy, the way CIRCULATE-US is, but at postadjuvant. If you’re still positive, and FOLFOX [5-fluorouracil, leucovorin, oxaliplatin] or capecitabine-oxaliplatin in stage III did not take care of your ctDNA [circulating tumor DNA], that would be a different therapy. A targeted therapy such as BRAF-directed therapy for BRAF V600E altered, HER2 [human epidermal growth factor receptor 2]–directed therapy if you’re HER2 amplified, immunotherapy if you’re MSI [microsatellite instability]–high. Or if you don’t have a biomarker, just giving FOLFIRI [5-fluorouracil, leucovorin, irinotecan] had an impact when FOLFOX [5-fluorouracil, leucovorin, oxaliplatin] wasn’t able to clear the ctDNA. Those are just 2 of many globally, but we’re all happy to field specific questions around that offline.

Tanios S. Bekaii-Saab, MD: One aspect about your study that I love is that it doesn’t look at just switching chemotherapy or intensifying chemotherapy, which has certain limitations. If you’re not doing well with 1, why would you do better with by switching the chemotherapy? Now that we understand that there are a lot more biologic switches that we can turn off—the earlier, the better—your study addresses this nicely. Fingers crossed that it ends up being more impactful than a switch of the chemotherapy.

Transcript edited for clarity.

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