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Should Anthracyclines Be Given in Advanced Gastroesophageal Cancer?

Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Manish Shah, MD, Weill Cornell Medical College; Ian Chau, MD, Royal Marsden Hospital
Published: Monday, Dec 05, 2016


Transcript:

Johanna Bendell, MD:
There has been a lot of discussion about what else can we add to locally advanced therapy to make it better or worse. In the MAGIC studies, you use anthracyclines. There’s been some discussion now in the metastatic setting, do we still need to use anthracyclines? I want to take a poll. I’m going to start with Ian, but I’m going around the table, and I want you to say yes or no, both for locally advanced and metastatic disease.

Ian Chau, MD: If we talk about locally advanced disease where we’re giving palliative chemotherapy, we’re still following the paradigm of MAGIC, so therefore, we will routinely consider giving triplet epirubicin/cisplatin, often in connection with capecitabine. When we move to metastatic disease, a triplet is really for fit patients. So, I think the number-one thing to decide is what is the performance status and what are the comorbidities. Certainly, if they have comorbidity, which is a contraindication to anthracycline, then we would not give it. Now, for a very fit patient, the next thing is whether you have to give a triplet. My own opinion is that I don’t have to, and also I believe that in clinical trials, to add an extra drug onto a triplet is getting very difficult because we are already reaching the maximum tolerated dose with the three drugs. You’re adding an extra novel agent. That usually takes the patient over the limit. I think a lot of times when we’re looking at new drugs, novel drugs we’re trying to bring in, I probably would favor more a two-drug platform and then add in the new agent. So, certainly, I think epirubicin is an option. I don’t think it’s the essential option.

Johanna Bendell, MD: Okay. Poll number 2, Yelena.

Yelena Janjigian, MD: It’s very refreshing to hear that.

Ian Chau, MD: We have insights.

Yelena Janjigian, MD: It’s funny because David Cunningham at ASCO, after presenting OEO5 data, clearly stated that the role of epirubicin is diminishing in both the treatment of metastatic and even locally advanced disease. I will start with the easier question to answer. For metastatic disease, there’s really no role for epirubicin. Even NCCN guidelines have recently changed. In fact, members of the gastric thought leaders, Jaffer Ajani, myself, Dan Catenacci, and several others have actually recently published a statement piece in the JCO trying to put an end to routine use of epirubicin in the metastatic setting. Ian’s point is excellent: it’s a hard regimen to build on with biologic therapy, and it also limits your ability to get second- and third-line therapy. What I tell my metastatic patients is that this is a marathon, this is not a sprint. We have to strategize and plan ahead for second-line, third-line, and so on therapy, and I think a doublet in the first-line therapy allows you to do that.

With locally advanced disease, the data are softer, I would say, but more and more, particularly for GE junction tumors, epirubicin has really lost track with the OE05 data. But I would probably not use it. I hardly ever use it in local advanced disease.

Johanna Bendell, MD: And certainly not in conjunction with radiation.

Yelena Janjigian, MD: Certainly not. But even for distal gastric cancer, the majority of these patients are older, nutritionally compromised, and just can’t get epirubicin.

Johanna Bendell, MD: Manish?

Manish Shah, MD: I echo what has been said already. I think that it’s been long recognized that epirubicin adds little. For me, I actually maybe was a longer hold out of using epirubicin because the MAGIC data in the curative setting were actually the best data of a 500-patient study, and it improved survival, and it actually was powered for survival and did its job. So, it was hard for me to take the step that maybe epirubicin isn’t used—although I have a very low threshold to not use it if someone has toxicity or if someone doesn’t tolerate it, then I drop that one first. But the OE05 data coming out, which was not in the same setting, esophageal cancer, not gastric cancer, it does sort of question the role of epirubicin in that disease. I think I’m using it less and less in the perioperative setting, although I still do use it.

In the metastatic setting, I think that you’ve alluded to it that there are actually increasing options for patients. It’s incredible! When I first started practicing, which wasn’t that long ago, patients sometimes didn’t get first-line therapy. They would come to me untreated, saying that my doctor didn’t think that there was more treatment. And now there’s second- and third-line, and some people are getting longer than that. So, really, the era is changing, and it’s really exciting. I find that there are other drugs, and so I really don’t use epirubicin in the metastatic setting.

Transcript Edited for Clarity
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Transcript:

Johanna Bendell, MD:
There has been a lot of discussion about what else can we add to locally advanced therapy to make it better or worse. In the MAGIC studies, you use anthracyclines. There’s been some discussion now in the metastatic setting, do we still need to use anthracyclines? I want to take a poll. I’m going to start with Ian, but I’m going around the table, and I want you to say yes or no, both for locally advanced and metastatic disease.

Ian Chau, MD: If we talk about locally advanced disease where we’re giving palliative chemotherapy, we’re still following the paradigm of MAGIC, so therefore, we will routinely consider giving triplet epirubicin/cisplatin, often in connection with capecitabine. When we move to metastatic disease, a triplet is really for fit patients. So, I think the number-one thing to decide is what is the performance status and what are the comorbidities. Certainly, if they have comorbidity, which is a contraindication to anthracycline, then we would not give it. Now, for a very fit patient, the next thing is whether you have to give a triplet. My own opinion is that I don’t have to, and also I believe that in clinical trials, to add an extra drug onto a triplet is getting very difficult because we are already reaching the maximum tolerated dose with the three drugs. You’re adding an extra novel agent. That usually takes the patient over the limit. I think a lot of times when we’re looking at new drugs, novel drugs we’re trying to bring in, I probably would favor more a two-drug platform and then add in the new agent. So, certainly, I think epirubicin is an option. I don’t think it’s the essential option.

Johanna Bendell, MD: Okay. Poll number 2, Yelena.

Yelena Janjigian, MD: It’s very refreshing to hear that.

Ian Chau, MD: We have insights.

Yelena Janjigian, MD: It’s funny because David Cunningham at ASCO, after presenting OEO5 data, clearly stated that the role of epirubicin is diminishing in both the treatment of metastatic and even locally advanced disease. I will start with the easier question to answer. For metastatic disease, there’s really no role for epirubicin. Even NCCN guidelines have recently changed. In fact, members of the gastric thought leaders, Jaffer Ajani, myself, Dan Catenacci, and several others have actually recently published a statement piece in the JCO trying to put an end to routine use of epirubicin in the metastatic setting. Ian’s point is excellent: it’s a hard regimen to build on with biologic therapy, and it also limits your ability to get second- and third-line therapy. What I tell my metastatic patients is that this is a marathon, this is not a sprint. We have to strategize and plan ahead for second-line, third-line, and so on therapy, and I think a doublet in the first-line therapy allows you to do that.

With locally advanced disease, the data are softer, I would say, but more and more, particularly for GE junction tumors, epirubicin has really lost track with the OE05 data. But I would probably not use it. I hardly ever use it in local advanced disease.

Johanna Bendell, MD: And certainly not in conjunction with radiation.

Yelena Janjigian, MD: Certainly not. But even for distal gastric cancer, the majority of these patients are older, nutritionally compromised, and just can’t get epirubicin.

Johanna Bendell, MD: Manish?

Manish Shah, MD: I echo what has been said already. I think that it’s been long recognized that epirubicin adds little. For me, I actually maybe was a longer hold out of using epirubicin because the MAGIC data in the curative setting were actually the best data of a 500-patient study, and it improved survival, and it actually was powered for survival and did its job. So, it was hard for me to take the step that maybe epirubicin isn’t used—although I have a very low threshold to not use it if someone has toxicity or if someone doesn’t tolerate it, then I drop that one first. But the OE05 data coming out, which was not in the same setting, esophageal cancer, not gastric cancer, it does sort of question the role of epirubicin in that disease. I think I’m using it less and less in the perioperative setting, although I still do use it.

In the metastatic setting, I think that you’ve alluded to it that there are actually increasing options for patients. It’s incredible! When I first started practicing, which wasn’t that long ago, patients sometimes didn’t get first-line therapy. They would come to me untreated, saying that my doctor didn’t think that there was more treatment. And now there’s second- and third-line, and some people are getting longer than that. So, really, the era is changing, and it’s really exciting. I find that there are other drugs, and so I really don’t use epirubicin in the metastatic setting.

Transcript Edited for Clarity
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