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Maintenance Therapy for 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: Wednesday, Dec 21, 2016


Transcript:

Johanna Bendell, MD:
We’re talking about treatment in the metastatic setting. In colorectal cancer, we see this concept of maintenance therapy. At one point, we were talking about stopping therapy and giving patients a break. And so, a lot of people are using this across the lines in terms of GI cancers. Manish, when you see a patient with first-line metastatic disease, do you talk about maintenance? Do you think about maintenance or stopping treatment or what would you do?

Manish Shah, MD: Great question. I think it comes up often. If you’re using FOLFOX, I think it’s very, very hard to give oxaliplatin for more than 4 or 5 months without having debilitating neuropathy, or fatigue, or other symptoms. So, I think there’s a natural way, then, to continue 5-FU, which I call less intensive therapy—which is also known as maintenance. I personally take the OPTIMOX data in colorectal cancer to heart, which basically, for me, showed that some treatment actually is helpful and taking a complete break in treatment may not be so good, between OPTIMOX-2 and -3. For me, I do use maintenance 5-FU. I think in the HER2-positive patients, I think it’s great to use maintenance Herceptin, very low toxicity. We’ll talk about this in the future, but ramucirumab has very low toxicity and might be another option for that, as well.

Johanna Bendell, MD: How about you, Yelena?

Yelena Janjigian, MD: I would agree that this is a tumor with aggressive disease biology, and you need to suppress the growth of micrometastatic or macrometastatic disease. And extrapolating from other solid tumors, such as colon or lung adenocarcinoma, continuing maintenance therapy or less intense therapy is very important. Unfortunately, there’s no level 1 evidence to support it. And, emotionally, it’s sometimes difficult for the patients to hear that, so occasionally we do give them an extra week or month off here and there, but it is important to continue it.

Johanna Bendell, MD: Yes, so no complete stops. Ian, same thing?

Ian Chau, MD: We have, actually, a completely different view because our standard is actually to stop after six to eight cycles. So, after 4 to 6 months, we actually stop treatment completely. That is the standard of care that we have been adopting. We do recognize the need to generate level 1 evidence. In fact, we are running a randomized study called PLATFORM at the moment in the UK, where the standard arm is to stop, and then we have maintenance capecitabine and then maintenance with a PD-L1 antibody.

So, we do want to try to generate the level 1 evidence to support or not support the use of maintenance therapy. Because, again, I think different countries, different patients, have different expectations and cultures. Because for us, to tell our patients that they’re not going to get a break, the first thing you say is, “I want to start you on chemotherapy,” and then they ask, “When can I go on holidays?” and that’s quite different. Whereas we also have some southern Europeans, and those patients actually perhaps behave more like United States patients. If you want to try to stop their treatment, they won’t let you. I think there are different cultures and different expectations, and in the end, we do need to generate that evidence.

But also, I think at that point, as Manish said, it is also a good timing to do clinical trials, as well, because patient already had a good period of chemotherapy, their disease is controlled, now you really want to see agents that really can extend the [favorable response] with, hopefully, low toxicity.

Manish Shah, MD: I was just going to say I think it’s fantastic that trial that you mentioned. In contrast, in the United States, the paradigm has always been to treat until progression even when we were giving really toxic treatment, which was really tough. And so, I think we’ve evolved to say, treat until progression, but less intensive therapy. So, that’s how that paradigm was a little bit different. But I think getting data and proving it is really helpful.

Transcript Edited for Clarity
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Transcript:

Johanna Bendell, MD:
We’re talking about treatment in the metastatic setting. In colorectal cancer, we see this concept of maintenance therapy. At one point, we were talking about stopping therapy and giving patients a break. And so, a lot of people are using this across the lines in terms of GI cancers. Manish, when you see a patient with first-line metastatic disease, do you talk about maintenance? Do you think about maintenance or stopping treatment or what would you do?

Manish Shah, MD: Great question. I think it comes up often. If you’re using FOLFOX, I think it’s very, very hard to give oxaliplatin for more than 4 or 5 months without having debilitating neuropathy, or fatigue, or other symptoms. So, I think there’s a natural way, then, to continue 5-FU, which I call less intensive therapy—which is also known as maintenance. I personally take the OPTIMOX data in colorectal cancer to heart, which basically, for me, showed that some treatment actually is helpful and taking a complete break in treatment may not be so good, between OPTIMOX-2 and -3. For me, I do use maintenance 5-FU. I think in the HER2-positive patients, I think it’s great to use maintenance Herceptin, very low toxicity. We’ll talk about this in the future, but ramucirumab has very low toxicity and might be another option for that, as well.

Johanna Bendell, MD: How about you, Yelena?

Yelena Janjigian, MD: I would agree that this is a tumor with aggressive disease biology, and you need to suppress the growth of micrometastatic or macrometastatic disease. And extrapolating from other solid tumors, such as colon or lung adenocarcinoma, continuing maintenance therapy or less intense therapy is very important. Unfortunately, there’s no level 1 evidence to support it. And, emotionally, it’s sometimes difficult for the patients to hear that, so occasionally we do give them an extra week or month off here and there, but it is important to continue it.

Johanna Bendell, MD: Yes, so no complete stops. Ian, same thing?

Ian Chau, MD: We have, actually, a completely different view because our standard is actually to stop after six to eight cycles. So, after 4 to 6 months, we actually stop treatment completely. That is the standard of care that we have been adopting. We do recognize the need to generate level 1 evidence. In fact, we are running a randomized study called PLATFORM at the moment in the UK, where the standard arm is to stop, and then we have maintenance capecitabine and then maintenance with a PD-L1 antibody.

So, we do want to try to generate the level 1 evidence to support or not support the use of maintenance therapy. Because, again, I think different countries, different patients, have different expectations and cultures. Because for us, to tell our patients that they’re not going to get a break, the first thing you say is, “I want to start you on chemotherapy,” and then they ask, “When can I go on holidays?” and that’s quite different. Whereas we also have some southern Europeans, and those patients actually perhaps behave more like United States patients. If you want to try to stop their treatment, they won’t let you. I think there are different cultures and different expectations, and in the end, we do need to generate that evidence.

But also, I think at that point, as Manish said, it is also a good timing to do clinical trials, as well, because patient already had a good period of chemotherapy, their disease is controlled, now you really want to see agents that really can extend the [favorable response] with, hopefully, low toxicity.

Manish Shah, MD: I was just going to say I think it’s fantastic that trial that you mentioned. In contrast, in the United States, the paradigm has always been to treat until progression even when we were giving really toxic treatment, which was really tough. And so, I think we’ve evolved to say, treat until progression, but less intensive therapy. So, that’s how that paradigm was a little bit different. But I think getting data and proving it is really helpful.

Transcript Edited for Clarity
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