An expert oncologist explains the combination subcutaneous injection therapy of pertuzumab, trastuzumab, and hyaluronidase-zzxf for patients with early-stage HER2+ breast cancer.
Sarah M. Tolaney, MD, MPH: Currently for our early-stage patients, certainly trastuzumab [Herceptin] and pertuzumab [Perjeta] is a standard in the pre-op [preoperative] setting for our stage II/III patients and trastuzumab and pertuzumab is also a standard in the first line for the metastatic HER2-positive setting where we give THP [docetaxel, trastuzumab, and pertuzumab] induction therapy really based on the CLEOPATRA [trial] data. We are using a lot of trastuzumab and pertuzumab currently, or at least previously we really only had the option of using IV [intravenous], trastuzumab, and pertuzumab. While highly effective and very well-tolerated, however, it does take quite a bit of time in the infusion center because upfront, you have to give a loading dose of therapy, which takes time, and then eventually you go onto maintenance. It's 2 different infusions of drugs that are given sequentially. It's really nice that there is now an opportunity to consider subcutaneous trastuzumab and pertuzumab, where both drugs are mixed into 1. In essence, you're giving 1 injection of both drugs, which can just be administered under the skin. Usually, this is an injection we're doing into the interior thigh. To me, this has been a tremendous difference because it's quick for the patient. They're in and out and really only in infusion for 5 to 7 minutes and they are not on the pharmacy side of things. It's a lot of work to give trustees for pertuzumab from a preparation standpoint and an infusion chair standpoint. And then from a patient perspective with the time in the chair and being in an infusion center. That has been huge for patients. We have data that has emerged that has really looked at this subcutaneous formulation. Initially, we saw data from the FeDeriCa study, which had really compared preoperative therapy with chemotherapy and IV HP [trastuzumab pertuzumab] to preoperative therapy with subcutaneous HP as Phesgo [pertuzumab, trastuzumab, and hyaluronidase-zzxf] and had looked at rates of pathologic complete response and had seen that they were really identical. They'd also looked at PK [paclitaxel] and looked at drug levels achieved, which are identical between the 2 arms. We have data to suggest these agents, whether you give it subcutaneously as Phesgo, or IV therapies [IV HP], from an advocacy perspective, it is equivalent, and from a pharmacokinetic standpoint, it is equivalent. But then we have data that came out of [the] PHranceSCa [study] that had looked at patient preference, which I thought was a super clever design because each patient got exposed to each formulation and then got to say what they preferred. They started with either Sub-Q, [subcutaneous] and then went to IV, or started with IV and went to Sub-Q. They surveyed patients for patient preference and then they got to choose which they wanted to stay on to complete the therapy after seeing both. Over 80% of patients preferred the subcutaneous formulation over the IV [formulation]. It tells us again, that the subcutaneous injection is just as effective as the IV therapy, but actually, patients prefer the subcutaneous injection. It’s so nice to actually have data to show that. Again, my approach has been when I'm giving IV HP to offer it to the patient instead of the subcutaneous formulation. This can be in the early pre-op setting where I'm giving TCHP [Taxotere (docetaxel), Carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab)] or it can be in maintenance after achieving PCR [pathological complete response] or they go on to get additional HP maintenance to complete their year of therapy. It’s really nice in that setting where patients are just coming in and out of infusion, otherwise, every 3 weeks for the HP, that they can just get subcutaneously and make a much quicker in and out transition.
Then in a metastatic setting, obviously we give induction THP, but after 6 or 8 cycles, people drop the taxine so they're really just coming in for the HP. And that is really nice so that they can just get the subcutaneous formulation. It also has an impact on IV access issues. Particularly in the metastatic setting where patients can need IV therapy for a long time, some people will get a port, but here I don't put ports in people just starting THP. It's really nice if they're getting Sub-Q HP, because again, then they're just in and out and don’t need to have a port, which obviously, has some risk of infection and clot. Certainly in the early-stage setting again, and those people getting HP maintenance, it's really nice that they don't even need an IV when they're coming in to get treatment. I think for multiple reasons, less time in the infusion chair, increases efficiency that way and its nice patients don't need ports. And again for patient preference, this has just been a really nice option. This is definitely something I discuss anytime I'm going to give an HP treatment.
Certainly, sometimes patients may have gotten IV therapy. Let's pretend someone got IV TCHP, but then they have a PCR and you want to switch them and just do subcutaneous trastuzumab and pertuzumab now because again, otherwise, they have no purpose for coming in for an IV placement anyway, they don't need chemotherapy. You certainly can do that. There's no washout period from having had an IV compared to just having had your last dose of Sub-Q. It's still the 3-week interval that you would use from your last dose of HP therapy, whether it was IV or Sub-Q to your next dose of therapy. There wouldn't be anything different that you need to do. You would not need to do again, any loading of the pertuzumab. You're just using the maintenance dose of the HP therapy since they've already been exposed. Again, no real difference in the patient, but nice for them not to need the IV with that transition.
Transcript edited for clarity.