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A conversation on gastric cancer at ESMO 2017: Part 1

Interview with Florian Lordick and Elizabeth Smyth

‘Filmed by PracticeUpdate with permission for inclusion on Advances in Gastrointestinal Cancer. More information and additional ESMO coverage can be found at www.practiceupdate.com

Interview transcript

Dr. Smyth: Good evening. I’m Dr. Lizzy Smyth. I’m a medical oncologist based at the Royal Marsden Hospital in London and I’m here tonight at ESMO 2017 with Professor Florian Lordick, a medical oncologist from University of Leipzig. Welcome, Professor Lordick.

So this evening we’ll discuss some developments in, I think, first the perioperative treatment of gastroesophageal cancer. Dr. Salah Al-Batran presented the data from the FLOT4 AIO study. Could you elaborate a little bit on those results for us?

Prof. Lordick: Yes. It was a randomized study in the field of resectable gastric and gastroesophageal adenocarcinoma, stages IB through III, and I mean, the standard was set 10 years ago by the crew you’re working with, by the Royal Marsden group, by the UK group, which set perioperative ECF or ECX as a standard of care. And the German group challenged the standard and randomized 700 patients to receive either FLOT, which is fluorouracil/leucovorin, oxaliplatin and docetaxel versus ECF or ECX. And first of all, we have to say that both perioperative chemotherapy regimens prove to feasible. The toxicities were comparable, some more epirubicin-associated toxicities in the ECF or ECX arm and some more docetaxel-associated toxicities like neuropathy or also hematologic and toxicities in the FLOT arm, but overall they were comparable.

And the important thing is that with treatment with FLOT, the overall survival of probability was increased and this result was significant with a 9% absolute difference after 3 years, which is certainly a very interesting result, and this went along without any increase in perioperative morbidity and mortality.

There is one interesting thing that was reproduced in the study and this is that the preoperative part of treatment was quite feasible. More than 90% received the whole duration of the preoperative chemotherapy, while in the postoperative setting only 50% of the whole population was able to tolerate all planned cycles of chemotherapy, with a trend to a better performance in the group of patients who was treated with FLOT.

There is an interesting and important subgroup analysis that was presented here, but also at ASCO, and this shows that the better efficacy associated with the FLOT study was almost consistent among all subgroups. So even if you look at the subpopulation presenting with esophageal cancer, Barrett’s cancer, or cardiac cancer or gastric cancer, FLOT was always better, and this seems also to be true for the different histological subgroups. There was an analysis presented here at this meeting, at ESMO, and it showed that for patients presenting the signet-ring cell cancers still FLOT was better than ECF and...

So, I’m curious to know your opinion how you will see this data in the light of the ESMO guidelines? You’re the first author of the ESMO recommendations on the treatment of gastric cancer, and what do the FLOT data mean for you?

Dr. Smyth: Well, I think the Guidelines Committee have reviewed the data, and of course, previously we recommended either a platinum or fluoropyrimidine doublet based on the ACCORD trial, or triplet ECX based on the results of the MAGIC trial. And I think that the FLOT data are certainly superior to MAGIC, and this is a paradigm shift in the treatment of perioperative operable gastric cancer; therefore, an update will be published of the guidelines, I hope, soon, and this should be recommended as a standard of care. Do you think that it will be widely adopted, FLOT, as a perioperative regimen?

Prof. Lordick: Well, actually, I have talked to many investigators from different countries and we are also active in the internationally active study groups like the EORTC, and my simple answer would be yes. I’ve heard a lot of positive opinions about these data and also with ongoing studies like the Multinational Talk Year study or the EORTC INNOVATION study, we are doing amendments and we are integrating FLOT into these study treatments, and I believe that there will be a rapid uptake of FLOT.

Of course we have to say that in Germany we have a lot of experience with this regimen, for other countries it’s new. Every regimen has its own learning curve, so I would recommend investigators and also physicians to be careful to monitor these patients closely until there is more experience with that, and there’s certainly a population of more frail patients, maybe also some elderly patients who are not the optimal candidates for FLOT, but in general words, I would say that this is recommendable standard regimen for everyone among Europe.

Dr. Smyth: You made a very good point, and this is true for all perioperative chemotherapy regimens, that we do have some difficulty completing the postoperative component perhaps for 50% of patients who their performance status is quite challenging in the postoperative period. There was some discussion at the oral abstract session surrounding whether we should give all the chemotherapy up front. What do you think about this as an approach?

Prof. Lordick: I would be cautious with such an approach. Currently we have robust data that a preoperative treatment duration of 8 to 9 weeks, it was 8 with FLOT, it was 9 weeks with ECF/ECX, improved survival results. Now shifting more into the preoperative field is a matter of research.

It’s interesting to do these studies, but adopting this for clinical practice I would recommend against that because we don’t know yet if longer periods of preoperative treatment don’t bring the patient into a worse condition. There are some data that cardiopulmonary function may be impaired, and there may be also negative impact on the immune system. I’m very happy to treat my patients for 8 to 9 weeks, but outside of the framework of clinical studies, I would not prolong the duration of preoperative therapy at the current time point.

Dr. Smyth: I think that’s a very reasonable point because we know that all the trials through which perioperative chemotherapy were developed were on an intention-to-treat basis and the survival results were irrespective of whether the patient received the postoperative component of treatment.

Prof. Lordick: Absolutely not.

Dr. Smyth: Are there any other approaches that we can think about risk stratification in the perioperative setting?

Prof. Lordick: I mean, one important point comes from your study group. You published a nice analysis on the outcomes of patients who do not achieve a good response during the perioperative treatment phase, and I like this paper very much that you published in the JCO, and I also made a comment on it in this journal. And the message for me is that patients who do not achieve a good response during the preoperative treatment phase who end up with a nodal positive stages or poor tumor regression stages, they have a very poor prognosis and so probably we should focus on that subpopulation with a poor prognosis more, and we are doing that in the EORTC study group, right?

We are currently writing a protocol giving the patients a chance to receive first operative immuno-oncology agents. This is certainly one way to think about that, and also certainly we need to focus more on histology and on molecular classifications, but this is really for future research to have maybe in the future different strategies for intestinal subtype, diffuse subtype, for genomically stable and unstable tumors, for MSI tumors, patients who really are a very special subgroup who may not benefit from perioperative treatment. All this has to be investigated.

But for the current time point, I would say, like you recommended in the ESMO guidelines, that perioperative chemotherapy is a standard and FLOT is the recommendable regimen.

Dr. Smyth: Agreed. These are important questions, but they can only be answered in the context of a clinical trial.

Prof. Lordick: Yeah.

Dr. Smyth: Thank you for coming, Florian, this evening.


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