DR KROP: PFS was the primary endpoint, and the data that was presented showed a very impressive PFS benefit with a hazard rate of about 0.6, going from a PFS of about 12 months in the control, which is a very reasonable and comparable PFS rate, to 18 months for the patients who got pertuzumab. And there was a similar improvement in survival, which didn’t technically meet statistical significance but certainly we would expect that it will be significant given a little bit more follow-up. So I think everybody was pretty impressed by the data.
DR LOVE: Dan?
DR HAYES: The one thing that has struck me about this study is that there’s not a third arm, pertuzumab alone. Is there any possibility that this is just a better drug than trastuzumab? And so that the combination is not better than pertuzumab alone? In terms of expense, if we put these two drugs together it’s going to break the bank.
DR KROP: Yes. No, I think that that’s a very important issue, and the data is now pretty clear and it gets back to this mechanistic issue, which I don’t think we have an absolutely firm handle on. But the data in the metastatic setting is that pertuzumab — the first study was done with pertuzumab and trastuzumab together, and as Kathy pointed out, that had very impressive, certainly respectable response rate of about 25 percent with a 50 percent clinical benefit — but in that same study, they did a cohort of pertuzumab alone, which showed a single-digit response rate.
And if you took those patients — and this is a very small number of patients — if you took those patients and added trastuzumab back to the patients who were progressing on pertuzumab alone, you saw a bump in the response rate, back up to 25 percent. So that was fairly convincing data. And as far as I know, it’s the only study that’s looked at a situation where patients have progressed on both of the single drugs, and because all the patients were trastuzumab progressors before they even went on the study. So they progressed on both, the single agents, and when you put them together you got a response. So I think that was pretty impressive.
DR HAYES: And where is that? Is that published?
DR KROP: It’s in press.
DR HAYES: Where?
DR KROP: In JCO. And then we have the data we talked about from the neoadjuvant setting, in the NEOSPHERE data, trastuzumab alone with chemotherapy was, and pertuzumab alone with chemotherapy, both were inferior to the combination. So it really does look like there’s synergistic interaction between these two. Exactly how that works, I think that’s something that’s going to need to be further studied.