Factors Determining Initial Treatment Approach for Gastric Cancer

Transcript:Johanna C. Bendell, MD: Thinking about your initial approach, you have a patient who has come in with metastatic disease. How do you approach treatment initially, David?

David H. Ilson, MD, PhD: I think for metastatic disease, chemotherapy really is the mainstay of treatment. I think our Japanese colleagues made a very important contribution with a trial called REGATTA, in which they actually looked at whether gastrectomy contributed to outcomes. Should patients with small-volume metastatic disease undergo gastrectomy first and get chemotherapy later, or just get chemotherapy? That study actually showed no survival advantage with gastrectomy. And actually, patients did worse when they got the gastrectomy. They had poorer chemotherapy tolerance.

For metastatic disease, we typically start with chemotherapy. There is global consensus that we combine a fluorinated pyrimidine with a platinum agent. Increasingly, oxaliplatin has become the platinum agent of choice, both for convenience and toxicity. Some randomized trial data consistently show better outcomes with oxaliplatin over cisplatin-based treatment. Whether we do infusional 5-FU [5-fluorouracil], which can be typically a 24- or 48-hour schedule every 2 week, we really have moved away from the 4- or 5-day infusion schedule.

Oral fluorinated pyrimidines, which would be capecitabine in the West or S-1 [tegafur-gimeracil-oteracil] in Japan, are probably of comparable efficacy. A fluorinated pyrimidine plus a platinum agent would be frontline treatment, and there are responses in about 50% of patients. A patient is usually on treatment for about 6 months, with median survival times of about 10 months. We’ll talk later about salvage options and whether we should consider incorporating other agents, other chemotherapy agents, into frontline treatment. There’s pretty much consistency, I think in practice, globally now.

Johanna C. Bendell, MD: What do you think, Dr Shitara?

Kohei Shitara, MD: Yes, the treatment strategy in metastatic disease is very similar. We do not use triplet regimens because our Japanese JCOG trial did not show the benefit of DCS, [docetaxel, cisplatin, tegafur-gimeracil-oteracil], in terms of over survival and PFS [progression-free survival]. We usually use doublet chemotherapy, including our S-1 [tegafur-gimeracil-oteracil] or capecitabine, or mainly oxaliplatin. We also use infusional 5-FU [5-fluorouracil] if the patient has dysphagia. So I think it’s very similar.

Going back to the previous question regarding PD-L1 [programmed death-ligand 1] and MSI [microsatellite instability]—high, MSI testing, I do so routinely. I look at testing for PD-L1, MSI, as well as NGS [next-generation sequencing] in a few cases. PD-L1 is still controversial, but I think this is 1 of the critical factors. This information may change a treatment strategy. So I think they’re very similar.

Johanna C. Bendell, MD: Very similar. It’s interesting because we have these chemotherapy regimens that we can use up front now that have relatively high response rates, decent response rates. It’s not leukemia, but there are decent response rates. We have a lot of patients who come in with GE junctional cancers or gastric cancers who are symptomatic for 1 reason or the other. Manish, do you think radiation plays a role here? Do you think our chemotherapy regimens are good enough? How do you approach these patients?

Manish A. Shah, MD: For metastatic?

Johanna C. Bendell, MD: Yeah.

Manish A. Shah, MD: That’s a great question. Radiation can play a role from a palliative standpoint. If you have a bleeding tumor, for example, that’s not an uncommon thing. You have a gastric mass that has some chronic blood loss, so you can do palliative radiation to help control the bleeding or as you start a systemic chemotherapy. GE [gastroesophageal] junction tumors can be associated with dysphagia. Often chemotherapy is actually active enough that it can lead to dysphagia relief quicker than with radiation. I don’t typically use radiation for the initial management of dysphagia. I try chemotherapy first.

There is some discussion about 3 drugs versus 2 drugs. I obviously agree that an oxaliplatin/5-FU—based treatment is the standard. There has been controversy because historically, epirubicin-platinum–5-FU [5-fluorouracil] was considered a very active 3-drug regimen. I just want to state for everyone and all our viewers that we really don’t think of epirubicin as active in gastric and esophageal cancers. It doesn’t add that much activity, and it adds a lot of toxicity. There was a randomized study in the neoadjuvant setting that compared cisplatin–5-FU [5-fluorouracil] versus epirubicin-cisplatin–5-FU [5-fluorouracil], and there was no difference in outcomes. Based on that, we really don’t use epirubicin.

The only other 3-drug regimen we would consider involves docetaxel. There is the FLOT regimen, F-L-O-T [5-fluorouracil, leucovorine, oxaliplatin, docetaxel]—which has a lot of activity, and we should talk about that further—as well as the DCF regimen, docetaxel-cisplatin—5-FU [5-fluorouracil]. People have done different modifications of it to make it more tolerable. The modified DCF [docetaxel-cisplatin–5-fluorouracil] regimen is very similar to FLOT [5-fluorouracil, leucovorine, oxaliplatin, docetaxel], except for cisplatin versus oxaliplatin. Those 2 regimens probably are a bit more active, in terms of response rates. Response rates are 50% to 55%. But Kohei made a very good point. When you are able to get second-line therapy, you end up getting all the drugs over the course of the patient’s care as opposed to putting it all up front. I think most of us think that’s why a 3-drug regimen may not be that important or that active. That’s also what we’re seeing here in the United States and in Europe. More and more people are getting second- and third-line therapy, so you may not need to use all your guns up front. I totally agree that a 2-drug regimen makes a lot of sense.

Transcript Edited for Clarity