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Relapse Following FLOT in Gastric/GEJ 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: Monday, Jul 17, 2017



Transcript:

Johanna C. Bendell, MD
: So, let’s say we’ve progressed, you’ve given FLOT, and the patient now has recurrence of disease. I’m going to ask you the same question you asked us before we started, and now it’s on you. Let’s say the patient relapses within 6 months. What are you going to do at that point, and all assuming HER2-negative?

Ian Chau, MD: If they relapse within 6 months, we would normally give these patients, who actually failed the neoadjuvant therapy, adjuvant chemotherapy. So, these are people who essentially are moving on to what we would normally deem as second-line chemotherapy for advanced disease, except the problem now is you use up all the active drugs. You used up your taxanes, your used your platinum, you used your fluoropyrimidine. In this situation, I think the other agent that we would normally turn to is probably irinotecan, which is also an active agent that has been shown in a Japanese Western Japan Oncology Group trial to be similar to weekly paclitaxel and also in the much smaller German AIO study that showed to improve overall survival as well as the Korean study. Irinotecan certainly is an active agent here, so I think that is something that we would consider using.

Another active agent in second-line we normally think of is ramucirumab. The ramucirumab trial is added then on its own: ramucirumab on its own or ramucirumab/paclitaxel. So, the question I suppose is if you’re going to choose between, if you’re going to give irinotecan versus ramucirumab on its own, which one would you use, because you could potentially use either? You probably prefer to use both, but there are no prospective data reported yet, as far as I understand, in gastric cancer. Obviously, FOLFIRI/ramucirumab is a regimen used in colorectal cancer, but in gastric cancer, there are no data available with combining the 2. I suppose at this stage, you want to know what the status of the patient is.

Obviously, irinotecan is associated with more cytotoxic drug side effects. You’re going to get more diarrhea, you’re going to get more neutropenic sepsis and other GI toxicity like nausea, vomiting. Whereas, we know ramucirumab in the REGARD study on its own has very, very few side effects. In fact, the side effect profile is very similar to just placebo. So, tolerability is similar, and the median survival—of course, this is a cross-trial comparison—is similar. But the other thing you can also think about is, if people fail docetaxel, it doesn’t mean they’d fail paclitaxel, so can you reuse that regimen of paclitaxel plus ramucirumab. Do we think there’s a true synergy between the 2 and then you really should think about going back and using a taxane with the ramucirumab? I think on that matter, I’m really quite interested in hearing the other panel members and see what they think.

Johanna C. Bendell, MD: It’s awesome, it’s a data-free zone—what you feel in your gut, no pun intended. Manish?

Manish A. Shah, MD: Right, unburdened by data. I think that you have to use irinotecan or FOLFIRI. I think if you have recurrence within 6 months or maybe even within a year after doing a FLOT regimen in the perioperative setting, you have to go to another cytotoxic. You make a good point about ramucirumab, but if you’re recurring within a year, you probably have very aggressive biology. I’m not sure that those same data would apply as monotherapy ramucirumab. I think I would probably do a FOLFIRI-type regimen.

Transcript Edited for Clarity

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Transcript:

Johanna C. Bendell, MD
: So, let’s say we’ve progressed, you’ve given FLOT, and the patient now has recurrence of disease. I’m going to ask you the same question you asked us before we started, and now it’s on you. Let’s say the patient relapses within 6 months. What are you going to do at that point, and all assuming HER2-negative?

Ian Chau, MD: If they relapse within 6 months, we would normally give these patients, who actually failed the neoadjuvant therapy, adjuvant chemotherapy. So, these are people who essentially are moving on to what we would normally deem as second-line chemotherapy for advanced disease, except the problem now is you use up all the active drugs. You used up your taxanes, your used your platinum, you used your fluoropyrimidine. In this situation, I think the other agent that we would normally turn to is probably irinotecan, which is also an active agent that has been shown in a Japanese Western Japan Oncology Group trial to be similar to weekly paclitaxel and also in the much smaller German AIO study that showed to improve overall survival as well as the Korean study. Irinotecan certainly is an active agent here, so I think that is something that we would consider using.

Another active agent in second-line we normally think of is ramucirumab. The ramucirumab trial is added then on its own: ramucirumab on its own or ramucirumab/paclitaxel. So, the question I suppose is if you’re going to choose between, if you’re going to give irinotecan versus ramucirumab on its own, which one would you use, because you could potentially use either? You probably prefer to use both, but there are no prospective data reported yet, as far as I understand, in gastric cancer. Obviously, FOLFIRI/ramucirumab is a regimen used in colorectal cancer, but in gastric cancer, there are no data available with combining the 2. I suppose at this stage, you want to know what the status of the patient is.

Obviously, irinotecan is associated with more cytotoxic drug side effects. You’re going to get more diarrhea, you’re going to get more neutropenic sepsis and other GI toxicity like nausea, vomiting. Whereas, we know ramucirumab in the REGARD study on its own has very, very few side effects. In fact, the side effect profile is very similar to just placebo. So, tolerability is similar, and the median survival—of course, this is a cross-trial comparison—is similar. But the other thing you can also think about is, if people fail docetaxel, it doesn’t mean they’d fail paclitaxel, so can you reuse that regimen of paclitaxel plus ramucirumab. Do we think there’s a true synergy between the 2 and then you really should think about going back and using a taxane with the ramucirumab? I think on that matter, I’m really quite interested in hearing the other panel members and see what they think.

Johanna C. Bendell, MD: It’s awesome, it’s a data-free zone—what you feel in your gut, no pun intended. Manish?

Manish A. Shah, MD: Right, unburdened by data. I think that you have to use irinotecan or FOLFIRI. I think if you have recurrence within 6 months or maybe even within a year after doing a FLOT regimen in the perioperative setting, you have to go to another cytotoxic. You make a good point about ramucirumab, but if you’re recurring within a year, you probably have very aggressive biology. I’m not sure that those same data would apply as monotherapy ramucirumab. I think I would probably do a FOLFIRI-type regimen.

Transcript Edited for Clarity
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