Jens Marquardt, MD, and Jens Hoeppner, MD, on Esophageal Cancer: Phase III Findings on Chemotherapy vs Chemoradiation

Marquardt: Good morning and thank you very much for being here today. It's a great pleasure to have you here and talk about the ESOPEC trial that you are presenting at this year's ASCO. Do you want to start out by just simply explaining why you actually did this trial to start with? Hoeppner: Locally advanced esophageal adenocarcinoma is usually treated in a multimodality treatment I've seen. And we've seen that both neoadjuvant chemoradiation and perioperative chemotherapy were superior to surgery alone. That has been stated in different trials, but there is no head-to-head comparison. So we don't know what to recommend to our patients, either neoadjuvant chemoradiation, or perioperative chemotherapy. And ESOPEC is the first head-to-head comparison of the recent protocols of perioperative chemotherapy, namely FLOT, and the recent protocol of neoadjuvant chemoradiation, namely CROSS. Marquardt: I think that makes a lot of sense. Can you tell us what the setup of the study was? How many sites were involved, how you approached everything? Hoeppner: ESOPEC was carried out between the years 2016 and 2020 in Germany. With overall 25 participating sites. We've enrolled 438 patients, and we've done follow up until 2023. Marquardt: Quite a big study. Right? Hoeppner: Yeah. Marquardt: Very, very nice. And can you tell us the key results and the key implications that you had from this trial? Hoeppner: In our trial, the primary endpoint was overall survival, and secondary endpoints were complications and adverse events from both treatment teams. And we found in the primary endpoint superiority of FLOT over CROSS with a hazard ratio of 0.7. That means after three years, the patients in the FLOT group had a survival benefit of 30% compared to CROSS. Marquardt: When you think about the key results, do you think there's anything that is particularly worth mentioning with regards to the toxicity or when you compare CROSS versus FLOT? Hoeppner: We have found nearly equal complication rates after surgery for both groups. And we have not, the complete adverse events shows that toxicity will be, as an endpoint we haven't addressed completely yet, but it looks like that we have quite equipoise in larger than grade three adverse events. Marquardt: And the surgery was similarly achieved in both arms? So there was no difference. Hoeppner: Yes, no difference in surgeries. Marquardt: I think that is very important, right? For such a trial. When you further think about implications of the trial, what's your, I mean, the overall in general key take messages that you have from the trial? Hoeppner: With the results from ESOPEC, we have a first statement that perioperative chemotherapy is superior to neoadjuvant chemoradiation, and I think we should recommend this to our patients and recommend perioperative chemotherapy with the FLOTS team for treatment of locally advanced resectable esophageal adenocarcinoma. Marquardt: This really is practice changing, right? So I assume that the radiation oncologist would have lots of questions to you with regards to the trial. In the design of the trial, did you account for differences in radiation or was that all investigator's choice or how was that adjusted? Hoeppner: The radiation scene was CROSS. This is established, or it was published in 2012 by a Dutch group. And this became the standard of care in Germany where the trial took place. And the participating centers were all university medical centers and large tertiary referral centers. So that this team was very established in the moment ESOPEC took place and therefore it was a standard of care in university medical centers in Germany and as participating centers. Marquardt: All experienced centers? Hoeppner: Yes. Marquardt: So more or less comparable approaches. Hoeppner: Yeah. Marquardt: Very, very nice. Thank you very much for being here today and sharing your insights into this beautiful study. Congratulations and yeah, good luck. Hoeppner: Thank you very much. Yes.