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Curative Intent in Locally Advanced Gastroesophageal Cancer

Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Ian Chau, MD, Royal Marsden Hospital; Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Manish A. Shah, MD, Weill Cornell Medicine, New York-Presbyterian Hospital; Kohei Shitara, MD, National Cancer Center Hospital East, Japan
Published: Wednesday, Jul 12, 2017



Transcript:

Johanna C. Bendell, MD:
Esophageal, gastroesophageal junction gastric cancer—what’s your recommendation for the oncologist sitting out here watching this going, “Well, now what do I do?”

Yelena Y. Janjigian, MD: First, you have to figure out if the disease is curable. It’s curable until proven otherwise, and, in that case, you need to approach it in a multidisciplinary fashion. For esophagus cancer, radiation is an important part. You can get a sense for a disease biology with chemotherapy first, but radiation needs to be added at some point to help clear the margin. For GE junction, again, there’s a gray zone for the serotype 3 tumors that cross into gastric-cardia, and those I believe can be approached with chemotherapy alone. And then surgery is an important part of this equation. I don’t think radiation will play a strong role for gastric tumors. The radiation field is quite large and toxic, and it’s almost impossible to get the patients through it. So, for gastric cancer, it’s chemotherapy. The question of whether or not the field is now moving to do most of the chemotherapy preoperatively, it’s better tolerated, and then we are moving toward novel agents in adjuvant setting.

Johanna C. Bendell, MD: OK. So, the Japanese have by far the most experience with localized potentially curable disease. How would you approach these patients with these 3 types in Japan?

Kohei Shitara, MD: Still, we have a very small number of patients with GE junction tumor, less than 10% with a usual type of distal gastric cancer. Also, esophageal adenocarcinoma is a more rare disease. So, at first, I’ll try to focus on the type of gastric cancer, and historically, D2 gastrectomy is a standard surgical procedure for Japanese gastric cancer. It achieves almost a 50% of disease-free survival without any type of chemotherapy. And the recent trials clearly show their impact of adjuvant therapy after D2 gastrectomy. It also achieved a 70% of disease-free survival. Now, if we focus on the high, advanced disease such as node positive or large size of primary or lymph node metastases, these patients are associated with worse outcomes. So, more and more, our clinical trials are currently ongoing to involve neoadjuvant strategy to compare surgery followed by adjuvant to the neoadjuvant followed by adjuvant therapy for clinical stage III disease in Japan.

In terms of a triplet regimen, we are also doing the phase III trial for advanced disease to compare the triplet and the doublet. If you go back to their esophageal cancer, we have many patients with squamous type. For these patients, we currently use neoadjuvant approach based on their previous phase III trial conducted in Japan. And, currently, we have compared doublet neoadjuvant, triplet neoadjuvant, and chemoradiotherapy followed by surgery. So, this large clinical trial conducted in Japan gives us future steps as a clinical practice standard.

Johanna C. Bendell, MD: Yes, so you guys are actually going to solve the problem for us, right? So, for your squamous esophageal, you use chemoradiation therapy, which I think is what we do in the United States as well. And then for your adenocarcinomas, you’re going to say chemotherapy with a triplet, a doublet, or chemoradiation, which I think is going to help clarify a lot of this for us. But it’s always very important to say it’s followed by the adequate surgery for the gastric cancer to make sure that you get a D2 resection. I think that’s a big message that we need to send out as well to the audience about the importance of the correct surgery for this disease. Manish, your thoughts here.

Manish A. Shah, MD: I think Kohei actually mentioned a very good point. The 50% survival with surgery alone really speaks to the differences in the disease between Japan, the United States, and Europe, where with surgery alone, survival is really around 30% or less. So, the addition of perioperative therapy, chemotherapy, is certainly appropriate. I think the FLOT regimen is the appropriate regimen based on the data we see and the evidence that the 3-drug regimen is active, certainly for gastric cancer. And for esophagus cancer, certainly Taxol/carboplatin and radiation, as per the CROSS trial, is the standard, both for adenocarcinoma and squamous cell cancer.

And for the GE junction cancer, it’s very interesting. That’s actually where we thought it was most active in terms of efficacy, that’s where we see most of our patients, and that’s where we really are doing a lot of radiation. In fact, I think the answer is going to be in another clinical trial. The Germans are doing a phase III study of Taxol/carboplatin/radiation versus FLOT for esophageal cancer, and I think that will probably answer the question. I think that it is a team decision, as Yelena said. The surgeons will play a role in this as well. I’m hedging because I really don’t know the answer for me. I feel like I probably will use FLOT for GE junction.

Transcript Edited for Clarity

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Transcript:

Johanna C. Bendell, MD:
Esophageal, gastroesophageal junction gastric cancer—what’s your recommendation for the oncologist sitting out here watching this going, “Well, now what do I do?”

Yelena Y. Janjigian, MD: First, you have to figure out if the disease is curable. It’s curable until proven otherwise, and, in that case, you need to approach it in a multidisciplinary fashion. For esophagus cancer, radiation is an important part. You can get a sense for a disease biology with chemotherapy first, but radiation needs to be added at some point to help clear the margin. For GE junction, again, there’s a gray zone for the serotype 3 tumors that cross into gastric-cardia, and those I believe can be approached with chemotherapy alone. And then surgery is an important part of this equation. I don’t think radiation will play a strong role for gastric tumors. The radiation field is quite large and toxic, and it’s almost impossible to get the patients through it. So, for gastric cancer, it’s chemotherapy. The question of whether or not the field is now moving to do most of the chemotherapy preoperatively, it’s better tolerated, and then we are moving toward novel agents in adjuvant setting.

Johanna C. Bendell, MD: OK. So, the Japanese have by far the most experience with localized potentially curable disease. How would you approach these patients with these 3 types in Japan?

Kohei Shitara, MD: Still, we have a very small number of patients with GE junction tumor, less than 10% with a usual type of distal gastric cancer. Also, esophageal adenocarcinoma is a more rare disease. So, at first, I’ll try to focus on the type of gastric cancer, and historically, D2 gastrectomy is a standard surgical procedure for Japanese gastric cancer. It achieves almost a 50% of disease-free survival without any type of chemotherapy. And the recent trials clearly show their impact of adjuvant therapy after D2 gastrectomy. It also achieved a 70% of disease-free survival. Now, if we focus on the high, advanced disease such as node positive or large size of primary or lymph node metastases, these patients are associated with worse outcomes. So, more and more, our clinical trials are currently ongoing to involve neoadjuvant strategy to compare surgery followed by adjuvant to the neoadjuvant followed by adjuvant therapy for clinical stage III disease in Japan.

In terms of a triplet regimen, we are also doing the phase III trial for advanced disease to compare the triplet and the doublet. If you go back to their esophageal cancer, we have many patients with squamous type. For these patients, we currently use neoadjuvant approach based on their previous phase III trial conducted in Japan. And, currently, we have compared doublet neoadjuvant, triplet neoadjuvant, and chemoradiotherapy followed by surgery. So, this large clinical trial conducted in Japan gives us future steps as a clinical practice standard.

Johanna C. Bendell, MD: Yes, so you guys are actually going to solve the problem for us, right? So, for your squamous esophageal, you use chemoradiation therapy, which I think is what we do in the United States as well. And then for your adenocarcinomas, you’re going to say chemotherapy with a triplet, a doublet, or chemoradiation, which I think is going to help clarify a lot of this for us. But it’s always very important to say it’s followed by the adequate surgery for the gastric cancer to make sure that you get a D2 resection. I think that’s a big message that we need to send out as well to the audience about the importance of the correct surgery for this disease. Manish, your thoughts here.

Manish A. Shah, MD: I think Kohei actually mentioned a very good point. The 50% survival with surgery alone really speaks to the differences in the disease between Japan, the United States, and Europe, where with surgery alone, survival is really around 30% or less. So, the addition of perioperative therapy, chemotherapy, is certainly appropriate. I think the FLOT regimen is the appropriate regimen based on the data we see and the evidence that the 3-drug regimen is active, certainly for gastric cancer. And for esophagus cancer, certainly Taxol/carboplatin and radiation, as per the CROSS trial, is the standard, both for adenocarcinoma and squamous cell cancer.

And for the GE junction cancer, it’s very interesting. That’s actually where we thought it was most active in terms of efficacy, that’s where we see most of our patients, and that’s where we really are doing a lot of radiation. In fact, I think the answer is going to be in another clinical trial. The Germans are doing a phase III study of Taxol/carboplatin/radiation versus FLOT for esophageal cancer, and I think that will probably answer the question. I think that it is a team decision, as Yelena said. The surgeons will play a role in this as well. I’m hedging because I really don’t know the answer for me. I feel like I probably will use FLOT for GE junction.

Transcript Edited for Clarity
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