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First-Line Therapy in HER2-Negative Gastric Cancer

Panelists: Johanna C Bendell, MD, Sarah Cannon Research Institute ; David H Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center; Manish A Shah, MD, Weill Cornell Medicine; Kohei Shitara, MD, National Cancer Center Hospital East
Published: Tuesday, Jul 30, 2019



Transcript:

Johanna C. Bendell, MD:
I’ve got all these experts here. I’ve got people watching. I get asked this question all the time: What’s your regimen of choice? Everybody talks about a fluoropyrimidine and a platinum. But in your practice, what’s your approach? What do you give to your average patient with metastatic gastric cancer, HER2-negative, first line?

Kohei Shitara, MD: Usually we use S-1 [tegafur, gimeracil, oteracil potassium] plus oxaliplatin. Maybe this is 80% of patients. An additional 20% of patients receive 5-FU [5-fluorouracil] and oxaliplatin because of dysphagia or some symptom. Very few patients receive the monotherapy because of a poor performance status in the first-line setting.

Johanna C. Bendell, MD: Very good. Manish?

Manish A. Shah, MD: That’s right. I would say that, about 75% of the time, I do use FOLFOX [folinic acid, fluorouracil, oxaliplatin]. It’s a 2-drug, very active regimen. I think probably 5% to 10% of the time I use single-agent 5-FU [5-fluorouracil], and maybe about 10% or 15% of the time I do use a 3-drug regimen because of other features that David mentioned—a young patient who needs symptomatic relief, wants to be aggressive, and those sort of things. One thing to consider, and we’ll talk about this moving on, is that a lot of the studies that compared 3 drugs with 2 drugs were in an era when we didn’t have that many options. In our careers, we’ve gone from basically first-line treatment to first- and second-line treatment; to first-, second-, third-line treatment. And even fourth line. And so with more lines of treatment, it’s not clear that patients will be well enough to receive that many lines of treatment. That may be another consideration. I do think that in colon cancer there are clear data that the more drugs you use overall, the longer the survival. And I think that may be the case as well. The issue is just getting it there safely.

Johanna C. Bendell, MD: When you give your FOLFOX [folinic acid, fluorouracil, oxaliplatin] in the metastatic setting to patients with gastric cancer, do you consider the bolus 5-FU [5-fluorouracil]?

Manish A. Shah, MD: Yes, I do. With the FOLFIRINOX [folinic acid, fluorouracil, irinotecan, oxaliplatin] regimen, I don’t use the 3-drug regimen. But for a 2-drug regimen, I do.

Johanna C. Bendell, MD: Do you ever use FOLFIRI [folinic acid, fluorouracil, irinotecan] up front?

Manish A. Shah, MD: Very rarely.

Johanna C. Bendell, MD: How about you, David?

David H. Ilson, MD, PhD: I think, again, there’s a consensus. I think FOLFOX [folinic acid, fluorouracil, oxaliplatin] would be the initial up-front treatment. For some patients we would consider capecitabine-oxaliplatin if they’re really opposed to getting central access. I differ a little with the hair loss with irinotecan. I think FOLFIRI [folinic acid, fluorouracil, irinotecan] is a viable up-front option. For patients with neuropathy, patients who have gotten prior adjuvant oxaliplatin, I think FOLFIRI [folinic acid, fluorouracil, irinotecan] is a viable first-line regimen. And then HER2 patients would get trastuzumab on the every-2-week schedule.

Johanna C. Bendell, MD: If you did use capecitabine, there is another question that comes up a lot. We have 3-week capecitabine-oxaliplatin regimens. We have 2-week capecitabine-oxaliplatin regimens. We have ways to dose the capecitabine continuously. We have ways to dose it on and off. What are we to do?

David H. Ilson, MD, PhD: Yeah, I dose it 1 week on, 1 week off. My experience is that when patients get 2-week schedules, they have a much higher risk of hand-foot syndrome. In the context of trials, we typically will do 2 weeks on, 1 week off. Patients are on treatment for a while, and the hand-foot syndrome is not so much an issue over a few months. But if patients are on treatment, in the United States we tend to treat patients until progression. Patients can be on treatment beyond 6 months with 5-FU [5-fluorouracil] maintenance therapy.

Johanna C. Bendell, MD: I guess the 3-week regimen, if you’re using oxaliplatin, the dose changes too?

David H. Ilson, MD, PhD: Yeah, it’s a higher dose, but patients do seem to tolerate it. We start to see increasing risk of neuropathy. Typically, when patients get above 500, 600 mg/m2, you have to be very cognizant of that, and we usually will stop it.


Transcript Edited for Clarity

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Transcript:

Johanna C. Bendell, MD:
I’ve got all these experts here. I’ve got people watching. I get asked this question all the time: What’s your regimen of choice? Everybody talks about a fluoropyrimidine and a platinum. But in your practice, what’s your approach? What do you give to your average patient with metastatic gastric cancer, HER2-negative, first line?

Kohei Shitara, MD: Usually we use S-1 [tegafur, gimeracil, oteracil potassium] plus oxaliplatin. Maybe this is 80% of patients. An additional 20% of patients receive 5-FU [5-fluorouracil] and oxaliplatin because of dysphagia or some symptom. Very few patients receive the monotherapy because of a poor performance status in the first-line setting.

Johanna C. Bendell, MD: Very good. Manish?

Manish A. Shah, MD: That’s right. I would say that, about 75% of the time, I do use FOLFOX [folinic acid, fluorouracil, oxaliplatin]. It’s a 2-drug, very active regimen. I think probably 5% to 10% of the time I use single-agent 5-FU [5-fluorouracil], and maybe about 10% or 15% of the time I do use a 3-drug regimen because of other features that David mentioned—a young patient who needs symptomatic relief, wants to be aggressive, and those sort of things. One thing to consider, and we’ll talk about this moving on, is that a lot of the studies that compared 3 drugs with 2 drugs were in an era when we didn’t have that many options. In our careers, we’ve gone from basically first-line treatment to first- and second-line treatment; to first-, second-, third-line treatment. And even fourth line. And so with more lines of treatment, it’s not clear that patients will be well enough to receive that many lines of treatment. That may be another consideration. I do think that in colon cancer there are clear data that the more drugs you use overall, the longer the survival. And I think that may be the case as well. The issue is just getting it there safely.

Johanna C. Bendell, MD: When you give your FOLFOX [folinic acid, fluorouracil, oxaliplatin] in the metastatic setting to patients with gastric cancer, do you consider the bolus 5-FU [5-fluorouracil]?

Manish A. Shah, MD: Yes, I do. With the FOLFIRINOX [folinic acid, fluorouracil, irinotecan, oxaliplatin] regimen, I don’t use the 3-drug regimen. But for a 2-drug regimen, I do.

Johanna C. Bendell, MD: Do you ever use FOLFIRI [folinic acid, fluorouracil, irinotecan] up front?

Manish A. Shah, MD: Very rarely.

Johanna C. Bendell, MD: How about you, David?

David H. Ilson, MD, PhD: I think, again, there’s a consensus. I think FOLFOX [folinic acid, fluorouracil, oxaliplatin] would be the initial up-front treatment. For some patients we would consider capecitabine-oxaliplatin if they’re really opposed to getting central access. I differ a little with the hair loss with irinotecan. I think FOLFIRI [folinic acid, fluorouracil, irinotecan] is a viable up-front option. For patients with neuropathy, patients who have gotten prior adjuvant oxaliplatin, I think FOLFIRI [folinic acid, fluorouracil, irinotecan] is a viable first-line regimen. And then HER2 patients would get trastuzumab on the every-2-week schedule.

Johanna C. Bendell, MD: If you did use capecitabine, there is another question that comes up a lot. We have 3-week capecitabine-oxaliplatin regimens. We have 2-week capecitabine-oxaliplatin regimens. We have ways to dose the capecitabine continuously. We have ways to dose it on and off. What are we to do?

David H. Ilson, MD, PhD: Yeah, I dose it 1 week on, 1 week off. My experience is that when patients get 2-week schedules, they have a much higher risk of hand-foot syndrome. In the context of trials, we typically will do 2 weeks on, 1 week off. Patients are on treatment for a while, and the hand-foot syndrome is not so much an issue over a few months. But if patients are on treatment, in the United States we tend to treat patients until progression. Patients can be on treatment beyond 6 months with 5-FU [5-fluorouracil] maintenance therapy.

Johanna C. Bendell, MD: I guess the 3-week regimen, if you’re using oxaliplatin, the dose changes too?

David H. Ilson, MD, PhD: Yeah, it’s a higher dose, but patients do seem to tolerate it. We start to see increasing risk of neuropathy. Typically, when patients get above 500, 600 mg/m2, you have to be very cognizant of that, and we usually will stop it.


Transcript Edited for Clarity
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