Our study was comparing two different approaches of neoadjuvant therapy in adenocarcinoma of the esophagogastric junction, one of them being chemoradiotherapy and the other approach being perioperative chemotherapy.
What was the study design?
The study design was to find out which of the two approaches would end up with a longer survival of the patients after that treatment followed by surgery, by complete resection of the tumours. That was the primary endpoint, of course we also had secondary endpoints such as progression free survival, such as tolerance of therapy or as the pattern of recurrence of the disease.
What were the results of this study?
The results were, for the primary endpoint, that the perioperative chemotherapy regimen, which consisted of FLOT which is 5FU, leucovorin, oxaliplatin and docetaxel, to be superior compared to the chemoradiotherapy approach which was exactly the regimen that was published by a Dutch group about 12 years ago, the so-called CROSS trial, consisting of carboplatin and paclitaxel.
What are the clinical impacts of these results?
The clinical impact is a clear advantage for the FLOT regimen in terms of what we used to be doing before the CheckMate-577 trial actually changed the standard of care. So we are comparing a regimen which is the original CROSS trial regimen which is outdated already but still it shows that the FLOT regimen, the perioperative chemotherapy, in itself is superior to the original design. We can assume that FLOT will be used in the future more often for that reason but we are anxiously waiting for results for the overall survival of the CheckMate-577 trial which tested the addition of immuno-oncology, which is an immune checkpoint inhibitor, to the Check regimen. Because some patients might not be fit enough for the FLOT regimen and for these patients the question is what is the second-best choice and we don’t know that yet but it could well be that the CROSS regimen, the chemoradiation, followed by durvalumab, which is the immune checkpoint inhibitor, after surgery could then be the second choice. But I think overall this has clearly shown that metastases can be better prevented by the perioperative FLOT regimen when not using an immune checkpoint inhibitor.
Are there any future studies you would like to mention?
There is one specific for Germany because FDG-PET CTs were not routinely or mandatorily done in this trial which is the case in many other countries. This reflected in 11 patients who developed FDG-positive tumour lesions classified as distant metastases in the planning phase of the radiotherapy. Therefore this tells us that before doing a local regional treatment modality in this disease this should have been mandatory and from now on we will be working to change that FDG-PET CT is done in such patients.
Another rationale which is clear is that we know that there are other regimens of chemoradiotherapy with more potent chemotherapy from a phase II trial and this showed promising results so we know that we should replace the original CROSS trial chemotherapy cocktail with a more potent chemotherapy. So we have learnt lessons of how to go on from this.
