Yelena Y. Janjigian, MD: In terms of systemic chemotherapy options for patients with metastatic disease, the approach is such that you’re improving their quality of life and survival and treating them as a chronic patient. It’s unlikely to cure them, but the idea is to keep them well, symptom free, and minimize the ill effects of the therapy to allow patients to live a longer and better life. The general approach is that we should minimize the toxicity of chemotherapy but also get the most response out of the agents that we have.

Either infusional 5-FU, fluoropyrimidine, or capecitabine are the backbone of this approach, similar to other GI tumors. We know that addition of platinum therapy, so a 2-drug combination, has been shown to improve quality of life, survival, efficacy, response, and so on. The 2-drug combination, 5-FU and oxaliplatin, is really the backbone of these clinical trials and for standard therapy.

Historically, with third drugs such anthracyclines, epirubicin, or a taxane, there are some data to support their use in combination to improve response. The toxicity from these agents is quite severe, and there have been several studies, modern studies, demonstrating that epirubicin really does not add anything in terms of efficacy to the 5-FU and platinum. There were several studies to show that FOLFOX or even FOLFIRI, which is 5-FU irinotecan, are equivalent in efficacy and survival, and much less toxic. Epirubicin can actually result in toxic-related death.

We do occasionally consider the addition of a taxane to the backbone of 5-FU and platinum, and this is in select patients. The treatment is generally considered only in young patients with large-volume symptomatic disease. And in patients for whom there’s no biologic therapy that we could add to 5-FU and platinum, a 3-drug combination could be considered.

There was even a recent consensus statement published in the Journal of Clinical Oncology with leaders in the field. This was in collaboration with Memorial Sloan Kettering, Dana Farber, and the University of Chicago, and really led by a group at MD Anderson saying that epirubicin should no longer be considered or ever used as first-line therapy in metastatic treatment for gastric or GE junction tumors.

Zev A. Wainberg, MD: The primary goals of therapy for metastatic or locally advanced unresectable disease, of both of these tumor types, is palliation. So, palliation is obviously of critical importance in patients who are metastatic. We know that they’re not going to be curable, a large majority of them, and so the goal of therapy is palliative.

Alan P. Venook, MD: The issue with gastric cancer, GE junction cancer, isn’t a lack of effectiveness of the chemotherapy, it’s whether it’s durably effective. And there have been a number of studies that have compared a variety of combinations. I actually favor FOLFOX, which is 5-FU, leucovorin, and oxaliplatin. That is a triplet or a doublet depending on how you consider the leucovorin. We use that pretty much as a backbone for our treatments, if we’re combining it with other biologics, or as monotherapy. Now, if you look at the studies, the studies have looked at combinations like ECX and EOX. That’s epirubicin, cisplatin, and capecitabine, or oxaliplatin instead of the cisplatin.

And more recently, there’s a combination called FLOT: 5-FU, leucovorin, oxaliplatin, and docetaxel. All of those have been used. In fact, the FLOT regimen appears to be a little bit better than the others in the neoadjuvant treatment of gastric cancer prior to surgery. But for advanced disease, I favor FOLFOX. It’s well tolerated. Patients with gastric cancer, certainly with advanced gastric cancer, are often malnourished and not in good shape. I think FOLFOX is the best tolerated of all those treatments.

In general, we use combination treatments. Even if it’s HER2-positive disease, we might treat it with a platinum and a fluoropyrimidine. If it’s HER2-negative, we would do something like FOLFOX or ECX or FLOT perhaps. All of these are multi-drug combinations. Again, the challenge is not so much to get a response, but to see if you can make it last.

Transcript Edited for Clarity