Jennifer Eads, MD, Abramson Cancer Center at Penn Medicine, Philadelphia, Pennsylvania, provides commentary on the results from the phase 3 ESOPEC trial, which found that perioperative chemotherapy with FLOT improved the survival for patients with resectable esophageal adenocarcinoma, when compared with neoadjuvant chemoradiation.

Dr Eads stated that these data “will definitely result in a new standard of care being established as perioperative chemotherapy being the way to go. That is a regimen that we also use in gastric cancer, so it will also make things more consistent across the entire upper GI space.

Transcript:

My name is Dr Jennifer Eads, I'm a GI medical oncologist and associate professor of medicine at the University of Pennsylvania Abramson Cancer Center.

The current treatment strategy for patients with a localized esophageal or gastroesophageal junctional adenocarcinoma can really be approached in 2 ways. It can either be done through treatment with neoadjuvant chemotherapy and radiation, followed by surgical resection, and then in those patients who have presence of residual disease in their pathologic specimen, adjuvant immunotherapy. Or it can be done via a perioperative chemotherapy approach with FLOT, which consists of 5-fluorouracil, oxaliplatin, and docetaxel, chemotherapy. Patients receive chemotherapy prior to surgery, then undergo surgical resection, and then receive the same FLOT regimen in the postoperative setting. There really has not been a comparative study that has looked at these regimens head-to-head to know which is the optimal strategy.

To date, the neoadjuvant chemoradiation approach and the perioperative chemotherapy approach have been considered relatively equivalent based on the Neo-AEGIS data. However, in that trial, they really did not have a large patient population that received optimal chemotherapy. They did not receive FLOT, which is really a more aggressive regimen. The ESOPEC trial is looking to further compare these 2 treatment modalities. The study was designed to randomize patients to receive either standard of care, neoadjuvant chemotherapy with carboplatin, paclitaxel, and radiation therapy, followed by surgical resection versus perioperative treatment with FLOT chemotherapy, which is 5- fluorouracil, oxaliplatin, and docetaxel.

This trial, the ESOPEC trial, is much cleaner in the sense that it's evaluating only 1 perioperative chemotherapy approach with FLOT chemotherapy. This trial aimed to look at whether or not there were significant improvements in survival outcomes between the 2 treatment arms. And what they determined was that there was a significant improvement in survival outcomes with the perioperative chemotherapy approach, as opposed to the neoadjuvant chemotherapy and radiation approach.

The results are actually quite striking, and so I think that it will definitely result in a new standard of care being established as perioperative chemotherapy being the way to go. That is a regimen that we also use in gastric cancer, so it will also make things more consistent across the entire upper GI space. Now it would be appropriate for patients with adenocarcinoma of the esophagus, the gastroesophageal junction, or the stomach to receive perioperative chemotherapy as the ideal treatment approach.

This definitely impacts how we study this disease going forward. Historically, we've used a lot of radiation therapy for patients with esophageal and GI in general adenocarcinoma. With these results, probably we will use a lot less of it. That being said, FLOT is a difficult regimen to receive. It's intense chemotherapy. It's 3 agents and not every patient is a good fit for that treatment. I can imagine that there will still be a space for people to receive something other than perioperative FLOT, which could be neoadjuvant chemotherapy and radiation.

I think that doing trials that are going to be solely looking at chemotherapy and radiation in the neoadjuvant space are now going to become much more challenging and we'll have to be more tailored to a patient population for which that is appropriate because we wouldn't want to not give people a lot if it has a known improvement in survival outcomes.

Source:

Hoeppner J, Brunner T, Lordick F, et al. The prospective phase III ESOPEC trial comparing perioperative chemotherapy to neoadjuvant chemoradiation in patients with esophageal cancer. Presented at 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #LBA1