Effect of MRD Positivity on Treatment Decisions in Colorectal Cancer
The expert panel discusses how MRD positivity affects treatment decisions for patients with colorectal cancer.
Transcript:
Tanios S. Bekaii-Saab, MD: Dan, how do you use MRD [minimal residual disease] assessment in your clinic?
Daniel H. Ahn, DO: I don’t use it routinely for all my patients. Hopefully this will be answered in future clinical trials: the importance of routine testing. But at this time, I use it on a patient-by-patient basis for specific scenarios. In cases where I know that it’s not going to necessarily change my management, as in this case given the absence of disease, I wouldn’t use it for a standard- or low-risk stage II colon cancer.
Tanios S. Bekaii-Saab, MD: Joleen, let’s assume this ends up being MRD positive. Everything else appears to be favorable—lymph nodes negative, adequate lymph node, LVI [lymphovascular invasion] negative, perineural invasion negative, microsatellite stable, etc—but it ends up being MRD positive. What would you do?
Joleen Hubbard, MD: I’d have a long discussion with the patient about the fact that we have evidence to say, “Patients who are ctDNA [circulating tumor DNA] positive postoperatively are at higher risk, and it’s very predictive for recurrence.” I’d also have a discussion about how we don’t know which chemotherapy to choose at this point. Do we proceed with a fluoropyrimidine alone, like 5-FU [5-fluorouracil] or capecitabine? Do we add oxaliplatin to that? If so, how long do we do it, 3 vs 6 months? There are a lot of unknowns of exactly how to treat the patient. If I had a ctDNA-positive stage II patient with no other risk factors, I’d urge the patient to receive adjuvant therapy and then have the discussion about how aggressive with the adjuvant therapy we want to be. I don’t know if I’d want to expose this patient to oxaliplatin. You may do well enough with the fluoropyrimidine alone and avoid the risk for neurotoxicity. But that question is unknown: how aggressive should we be with the chemotherapy at that point?
Tanios S. Bekaii-Saab, MD: Aparna, thinking about the scenario and the context of the DYNAMIC trial, that study was great to start with but a little confusing. Because we see our internal biases toward a more aggressive regimen with MRD-positive [disease]. The question in stage II disease is, do we need oxaliplatin, and do we need it for 3 or 6 months? If everything else aligns except for MRD, how would you integrate the previous knowledge, which didn’t integrate MRD assessment, with that patient in your clinic? It’s 3 vs 6 [months], oxaliplatin or no oxaliplatin.
Aparna Parikh, MD, MS: That’s such a tough question. Even with DYNAMIC, we saw a lot of patients getting platinum-based chemotherapy. This is a 55-year-old, and I still worry about an MRD-positive test. If you’re positive, it’s coming back. The approach I’ve taken even for stage II—this patient is 55, not an 80-year-old—is erring on the side of committing to 6 months of FOLFOX [5-fluorouracil, leucovorin, oxaliplatin], but I have a low threshold for dropping the oxaliplatin. There were compelling data in the stage III patients around early treatment—discontinuation and dropping oxaliplatin—for 8 cycles or so, which is when most patients are going to start to get into trouble with neuropathy. That’s been my approach. Capecitabine alone or 5-FU [5-fluorouracil] alone is totally manageable, but even in the stage III setting, I haven’t always loved capecitabine. My approach has been more of the 6 months of FOLFOX [5-fluorouracil, leucovorin, oxaliplatin] for higher-risk patients who are MRD positive, with the low threshold to drop the oxaliplatin at early signs of neuropathy.
Transcript edited for clarity.
