Assisting Community-Based Oncologists and Surgeons in Making Neoadjuvant Treatment Decisions for Patients with Early Breast CancerTolerability/toxicity issues with pertuzumab
2:50 minutes.
TRANSCRIPTION:
DR BLACKWELL: The good news is, we don’t see added cardiotoxicity, at least in the metastatic trials. So I think that was a concern. I think of pertuzumab as a second-generation HER2 antibody. It clearly interferes, HER2 binding with HER3. And although HER1/HER2 heterodimers are important, it’s kind of like that song, it’s all about the bass. It’s all about HER3. HER3 is the amplifier of the HER family, so the fact that pertuzumab has the ability to interfere with HER2/HER3 heterodimers, at least from an intracellular signaling, that’s probably the most important effect of pertuzumab. And there was this potential, because we know very little about trastuzumab-induced cardiac toxicity, that pertuzumab would add to it, and it does not. Everything is pointing to that it’s not. So the main side effects are really, I think, a result of HER2 being inhibited with HER1 signaling or — HER1 is also known as EGFR, for people who aren’t easily confused, like I am. It’s also EGFR. So the reality is that you see diarrhea. You can see a rash. My experience is that the rash is typically on the face and it is heat generated. Patients report it gets worse after the shower or being in the sun. And the most important thing about both of these is, the half-life of pertuzumab is quite long. So I frequently see patients getting these side effects, diarrhea, rash, and then the physician stopping it for a week or two and it doesn’t get better. And they’re like, “Oh. It must be something else,” and they restart it. Remembering that pertuzumab is a very long-acting antibody, so you have to manage what you perceive as its toxicities very differently than small molecule inhibitor HER1 side effects. DR LOVE: And when you talk about skin changes and diarrhea, when you think about EGFR, certainly in lung cancer, we have the EGFR tyrosine kinase inhibitors. You have the EGFR antibodies, like cetuximab/panitumimab, associated with skin and diarrhea problems. What you’re saying is that pertuzumab is kind of hitting the same part of the receptor. DR BLACKWELL: Absolutely. So it’s not terribly surprising we seeing an increase in incidence in both of those things when pertuzumab’s added. DR LOVE: How much of a problem is it? DR BLACKWELL: I can say that now that we’ve gathered more experience with it, I do have about 2, 3, now 4 people in my practice who we’ve actually had to drop the pertuzumab out because of the rash, in particular. It’s just as with all HER1 inhibitors, or EGFR inhibitors, it can be cosmetically very bothersome. It can actually get superficially infected and can be a real problem for patients. |