Subcutaneous HP Therapy in Early-Stage HER2+ Breast Cancer


Panelists review clinical data behind subcutaneous HP therapy in early stage HER2+ breast cancer and elucidate the real-world use of this approach.


Andrew Seidman, MD: I’ll use this as a convenient segue to ask VK about his experience with subcutaneous administration of HER2 [human epidermal growth factor receptor 2]. Can you speak about our foundation of data for that?

Vijayakrishna Gadi, MD, PhD: That’s a great question. Just to back up, what’s this new drug that we have? We call it Phesgo, but it’s standard pertuzumab and trastuzumab combined with hyaluronidase. When you inject those 3 drugs together into the skin, into the soft tissue, the hyaluronidase in that area gets degraded momentarily. The drug has a pocket to reside in and then it gets absorbed through the bloodstream gradually over a period of time. Within 24 to 48 hours, the tissue is repaired. It’s as if you were never there. The first benefit is that it’s a subcutaneous shot. The need for long-term usage of a mediport disappears with that. That’s a benefit not just in the adjuvant setting but potentially in the metastatic setting [as well]. The infusion time—the loading dose—is about 8 minutes, and the maintenance dose is about 5 minutes to deliver. It’s a slow injection. You’re taking a lot of chair time away.

Andrew Seidman, MD: Less time to chat with your patients in the chemotherapy area.

Vijayakrishna Gadi, MD, PhD: I’ll share a funny anecdote in a minute. The last thing is that they’ve done studies to show that it’s as good both in terms of getting to physiological end points and in terms of the drug levels and drug dose. If anything it’s a little better when you look at the randomized study evaluating this molecule. There’s been a patient preference study as well. In that study, 85% of the patients said, “I want my subcutaneous shot.” It was done in a nice way, so patients who were experienced with both were asked that question. In a number of measures, this has become a winner in this space for convenience and other things.

There are other considerations. We all practice in complex health care environments. A lot of things are going on with COVID-19 and trying to minimize people in the clinic. There are a number of other advantages, but frankly there are going to be financial considerations for some practices as well. In my experience, I’m a big fan. I’ve been at 2 institutions over this pandemic, and both adopted it. We’re using it. Patients seem to like it.

I’ll share this anecdote about a patient who was pregnant when she was diagnosed with HER2-positive disease. We got her through the preoperative therapy, she delivered, and she got to the adjuvant therapy. When it came time for her to go on the HER2+ targeting agents, we gave her 1 dose IV [intravenously]. Then the next dose she came back for, we gave it subcutaneously. She came back and said, “Can I go back to the IV?” We’re asking why, and she said it was the only time I got in the chair with myself. Otherwise, she had a little baby at home. There will be that exceptional patient that will make that choice for a consideration. We can’t quite figure out, but for the vast majority patients, this is a winner.

Andrew Seidman, MD: Some of our nurses enjoy that face time too. The FeDeriCa trial was interesting in that the PK [pharmacokinetic] analysis showed bioequivalence, and the pathologic CR [complete response] rates were virtually imposable.

Vijayakrishna Gadi, MD, PhD: Yes, the secondary end point. The path CR rate was the same.

Andrew Seidman, MD: Dr Graff, do you have experience in your clinic with this?

Stephanie Graff, MD: Yes, we just brought Phesgo [pertuzumab, trastuzumab, hyaluronidase] on formulary. I’ve had a very similar experience to VK. Everything he said is true. For all of us in leadership positions, it diminishes chair time for our patients, which helps in a crowded cancer center. It’s very helpful for managing the flow of your infusion center, especially when we’re trying to distance patients, manage all the issues of the pandemic, and maximize patient safety. There are a lot of benefits there. It’s also very well tolerated. We worry if the injection is uncomfortable, if there are skin reactions, if there’s irritation. But patients do great with it. I’ve had great luck transitioning patients to Phesgo [pertuzumab, trastuzumab, hyaluronidase] after the adjuvant-neoadjuvant part, in combination with that. Also in the metastatic space, patients on that long-term pertuzumab-trastuzumab maintenance cycle love being able to pop in and get a quick infusion.

Andrew Seidman, MD: The best way to decompress your oncology clinic is to keep patients at home. Tiffany, could you speak to some emerging data on home administration of this?

Tiffany Traina, MD: Sure, I’m happy too. Our colleague Chau Dang [MD] presented [at the American Society of Clinical Oncology Annual Meeting] on a study that is partly enrolled. The target accrual is about 200 patients, but they reported data on about 150 patients who were able to receive trastuzumab-pertuzumab subcutaneously at home. The pandemic drove a lot of innovation, and this was 1 of those opportunities where they had skilled home nurses trained in emergency protocols and had emergency equipment in the home if necessary. There were patient preference data from that as well as safety data. Fortunately, there were no concerning hypersensitivity reactions. Just a low grade 1 skin irritation, and patients extraordinarily preferred the convenience of home administration. There was time saved, less distress, being able to avoid going to a hospital or even an ambulatory care setting. Interestingly, in addition to just the administration of the drug at home, a subset in that protocol looked at home cardiac monitoring as well with echocardiograms. Overall, it’s nice to see that maybe a silver lining of the pandemic is driving innovation to allow our patients to have care where it’s more convenient for them.

Andrew Seidman, MD: A lot of good things have come out of these dark times of the pandemic that will carry over. We’re all living in that world of telemedicine. I’m happy to see that my colleagues are 3-dimensional, not just 2-dimensional on a Zoom screen. But innovation that comes out of desperation.

Transcript edited for clarity.

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