HER2-Positive Gastric Cancer

Transcript:Johanna Bendell, MD: Now, what about HER2-positive disease? Yelena, tell us a little bit about HER2-positive disease and how you use the treatment in the metastatic setting. Do you jump off the band wagon and do it with FOLFOX? And if you do, how do you dose it? A very common question, or do you use it, as Ian was alluding to, with maybe the big whack, a la the ToGA trial?

Yelena Janjigian, MD: So, for HER2, trastuzumab was FDA-approved based on the combination with capecitabine/cisplatin. Biologically, I don’t believe that capecitabine/cisplatin is any different from 5-FU/oxaliplatin. The backbone is similar, and there shouldn’t be any interaction, for example, biologically. If a patient is not going on a first-line study, then generally I do use it with FOLFOX, and I dose trastuzumab every other week with a 6 mg/kg bolus loading dose followed by 4 mg/kg every other week FOLFOX. It’s well tolerated, and we use it in a standard way. But there’s no level 1 evidence, certainly, to support it, but in my practice, it’s commonly done.

Johanna Bendell, MD: And here’s a very important question, one I get from a lot of referring physicians. I have a patient with locally advanced disease who I found out is HER2-positive. Should I give them trastuzumab?

Yelena Janjigian, MD: What do you say?

Johanna Bendell, MD: Clinical trial, of course.

Yelena Janjigian, MD: That’s right.

Ian Chau, MD: What is available to you in terms of clinical trials?

Johanna Bendell, MD: That’s a loaded question. So, most of the clinical trials are going on through the Cooperative groups within the United States right now.

Yelena Janjigian, MD: RTOG 1010, which is the carboplatin/paclitaxel, so it’s the CROSS trial plus/minus trastuzumab. That’s completed, but there are several trials that are in planning.

Ian Chau, MD: In Europe, we actually have a study called INNOVATION, which is run by the EORTC group and is essentially for HER2-positive patients. They get randomized to cisplatin plus fluoropyrimidine, usually we use capecitabine, and one of the arms is the addition of trastuzumab to the XP regimen. And the other arm is trastuzumab and pertuzumab added to that and given perioperatively. So, they give it before surgery and then after the operation for the HER2-positive patients.

Manish Shah, MD: Exactly. I think there’s a big impulse to use trastuzumab in the locally advanced setting, taking a cue from breast cancer, where the hazard ratios in the adjuvant setting are 0.65 or 0.60, which we’ve never achieved in gastric cancer or gastroesophageal cancer, unfortunately. So, I understand there’s the significant drive. However, I think as we’re learning and treating all these patients, we also realize that HER2-positive gastric cancer is not the same thing as HER2-positive breast cancer. The benefit with trastuzumab is not the same. The mechanism of resistance is not the same. For esophageal cancer, you’re irradiating the chest and with the use of Herceptin, you have to worry about safety and things like that. So, I think that outside of a clinical trial, which is probably always the right answer, I would just add a word of caution using a HER2-directed therapy in the neoadjuvant or adjuvant setting.

Transcript Edited for Clarity