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ASCO GI 2023 | FOxTROT: neoadjuvant FOLFOX chemotherapy in colorectal cancer
Jenny Seligmann, MBChB, PhD, University of Leeds, Leeds, UK, provides an overview of the Phase III FOxTROT trial (NCT00647530), which assessed neoadjuvant chemotherapy in patients with locally advanced colorectal cancer. Patients received either neoadjuvant FOLFOX followed by surgery and more chemotherapy, or the standard of care with only surgery and post-operative chemotherapy. Disease-free survival (DFS), the primary endpoint, was met, and patients with T4 tumors benefited the most, whereas microsatellite instability high (MSI-H) patients tended to have poorer outcomes. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Gastrointestinal Cancers (GI) Symposium in San Francisco, CA.
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Transcript (edited for clarity)
So the FOxTROT trial is the first trial to look at giving neoadjuvant chemotherapy in locally advanced colon cancer. So, of course, neoadjuvant treatment is the standard of care for many other cancers, including GI cancers, including gastric cancer. But this is the first time where we’ve tested giving neoadjuvant chemotherapy in colon cancer. The FOxTROT trial was really quite simple...
So the FOxTROT trial is the first trial to look at giving neoadjuvant chemotherapy in locally advanced colon cancer. So, of course, neoadjuvant treatment is the standard of care for many other cancers, including GI cancers, including gastric cancer. But this is the first time where we’ve tested giving neoadjuvant chemotherapy in colon cancer. The FOxTROT trial was really quite simple. What we were trying to do is to see whether giving systemic treatment earlier on in the patient journey will lead to tumor responses, will lead to better resections, surgical resections, but most importantly, to see whether we could increase the cure rate. So that was the main rationale behind the trial, and we had to just be very careful that we were also going to see that it was safe, there wasn’t any repercussions in terms of surgical safety as well. So that was an important consideration for the trial.
If I just discussed the design very quickly. So it was a very simple trial. Patients were radiologically staged to have locally advanced colon cancer, and what happened in the trial was either they had standard treatment, which was upfront surgery, followed by adjuvant chemotherapy, or in the novel arm of the trial, six weeks of planned chemotherapy was given ahead of the operation. So patients had six weeks of FOLFOX, they went for their surgical resection, and then after the operation, they continued the duration of adjuvant chemotherapy. So patients were randomized two to one. And what we saw was that the trial met its primary endpoint, and we did see a reduction in recurrences. So a 5% reduction in recurrences at two years in the patients who were treated with neoadjuvant chemotherapy. Other positive results were very consistent efficacy results in terms of tumor downstaging, and we found that it was safe so there wasn’t any more chemotherapy toxicity.
But really importantly, there wasn’t any additional surgical morbidity. If anything, there were fewer perioperative complications in patients who had neoadjuvant chemotherapy. The other really interesting thing was that we tried to understand, “Well, is there a group that really benefited the most from this approach?” Because this is a different whole patient pathway. And we found a couple of things. So patients with the most locally advanced tumors with T4 tumors seem to benefit most from upfront chemotherapy. And really importantly and consistently with all of the data with immunotherapy, patients with deficient mismatch repair or MSI-high tumors also appear to benefit less from upfront chemotherapy.