DR HECHT: The other things that have been looked at, particularly in breast cancer, that are now seeping into upper GI cancer, have been pertuzumab and T-DM1. T-DM1 has been a very frustrating agent for us, because we’ve been doing preclinical studies for many years and have been unable to set up the trials. But there are trials that are underway. T-DM1 as, actually, probably your audience knows better than the GI oncologist, is an ADC with trastuzumab with maytansine attached to it. At least in breast cancer, it’s a very active agent, though it does have some toxicity, but less toxicity than chemotherapy alone. And my feeling is that this will probably be the anti-HER2 agent to beat in the future, but we need to see, especially since the – at least the data in breast cancer look so good.
Pertuzumab is another agent that’s already been approved in breast cancer as well. That was 2C4. The funny thing is that was originally the control antibody in our old antibody tests against, actually, trastuzumab and in preclinical trials. It binds actually HER2 but prevents dimerization. And in a very expensive combination with trastuzumab also has very good activity in breast cancer. And these trials are underway.
So we have the one really biologically defined subgroup in upper GI cancer, which is HER2-positive. I think we have one drug that we already have, that we only have one indication, though many people would continue it and probably are continuing it second and third line. And we have a couple of really interesting combinations. As I said, the pertuzumab/trastuzumab combination is very interesting. I think T-DM1 is the one not just — it really is to replace chemo. I think — something I’m particularly interested in, rather than just adding it to chemotherapy, but also, as has been brought up, many of these patients are beaten up. And the ability to give a targeted type of chemotherapy is very attractive. So, in this subgroup, I think it’s very exciting, at least right now.
DR LOVE: Yes. Your colleague, Sara Hurvitz, has the paper, just came out in the JCO, looking at T-DM1 up front.
DR HECHT: Yes.
DR LOVE: I mean, there’s chemo in there, but the patients don’t have chemo problems. And it was better than docetaxel/trastuzumab. And the pertuzumab thing really surprised people, because the bump that they got by adding that onto trastuzumab and chemo was pretty substantial.
DR HECHT: For a drug that had failed in many respects by itself — with chemo —
DR LOVE: Right.
DR HECHT: — or chemotherapy. So yes. I think all of us are really surprised by that.