Assisting Community-Based Oncologists and Surgeons in Making Neoadjuvant Treatment Decisions for Patients with Early Breast CancerOverview of pertuzumab
3:32 minutes.
TRANSCRIPTION:
DR MAMOUNAS: Pertuzumab is what we call a dimerization inhibitor, so it binds in a different subdomain of HER2 as trastuzumab does. But the net outcome is that it prevents dimerization between HER2 and other HER2 receptors as well as HER2/HER1, HER2/HER3 and, at the end, blocks intercellular signaling. And preclinical data have shown that when you combine trastuzumab and pertuzumab, you get a synergistic effect. It’s interesting, because initially, when pertuzumab came out, the obvious question was, why not use pertuzumab by itself? But at the end of the day, the preclinical data, then supported by the clinical data, showed that actually using them together gets a much better effect than using each one alone. DR LOVE: Kim, can you talk a little bit more about the benefit, the additional benefit that you get when you add pertuzumab and why you think that happens? DR BLACKWELL: So the best data about pertuzumab come from the first-line, metastatic, HER2-positive breast cancer population where, in a study termed CLEOPATRA — and it’s such a great name. We now call the regimen the CLEOPATRA regimen — looked at a combination of docetaxel/trastuzumab — so that doublet or docetaxel/trastuzumab and pertuzumab. And in an over 800-patient study, half the women got just the two and half the women get all three, with the pertuzumab. There was a 15.8-month survival advantage. So that’s — if not the largest survival advantage we’ve ever seen in the history of breast cancer, to my knowledge, with the exception of a placebo-controlled study. I mean, to try to put that survival advantage into perspective, we see about a 4-month survival advantage adding trastuzumab to chemo, and we’re now adding pertuzumab to trastuzumab, and it’s 15.8-month survival advantage. And one of the things that’s even more impressive and probably very attractive for thinking about utilizing both of these antibodies, pertuzumab/trastuzumab, in the adjuvant setting is that, in the CLEOPATRA study, women only, on average, got about 6 cycles of chemo, and then the chemo was stopped. And then they continued on either getting both antibodies, pertuzumab and trastuzumab, or trastuzumab alone. And yet we see this tremendous, close to 16-month survival advantage, when most of these women were only on chemotherapy 15, sometimes 18 weeks. And so it really does speak to that there is a synergistic activity of using the 2 antibodies together in the treatment of HER2-positive metastatic breast cancer. DR LOVE: Now Terry, any hints about why this happens? I kind of was surprised when it first — as Kim said, there was such a big bump by adding the second monoclonal antibody. Any thoughts, or have you heard any theories about why there was such a big bump? DR MAMOUNAS: I don't know for sure, but obviously more complete blockade of the intracellular signaling. Obviously potential dimerization with other receptors, the HER1/HER3, so it’s more of a pan-HER inhibitor versus just HER2. And, in fact, we’ve taken this concept now even to a point that, even if you inhibit the ER pathway as well, potentially you may have even more efficacy because sometimes that’s a pathway that actually stimulates the tumor. Or maybe increasing the immune effect of trastuzumab, which is also probably one of the main reasons why it’s so effective. |