Subcutaneous Therapy for HER2+ Breast Cancer

Lisa A. Carey, MD, FASCO: Reshma, you raised an important thing that’s not specific to HER2-positivemetastatic breast cancer, but I’m sure you all saw the presentation at ASCO 2021 [American Society of Clinical Oncology annual meeting] of the patient-centered dosing initiative. It was discussed in the oral session on Saturday. Led by patient advocates with a medical advisory board for study design, it was basically a survey of more than 1200 women with the appropriate representation of metastatic HER2+ breast cancer, who had, for the most part, been on therapy for 1 to 5 years. They were patients with ongoing metastatic breast cancer and had received a lot of different drugs. The upshot was that two-thirds of them, or it was more than 80%, had some sort of adverse effect. Most had had dose reductions, dose delays and had to go through these things. At the end of the day, the call to arms for us in the medical community was that 92% of the patients said, “We want you to individualize our dose. We do not want you to start at a maximum tolerated dose and then back off. We do not like that. It’s not helping us. We want you to get smarter about this.” I think that’s something we should take to heart.

Vijayakrishna Gadi, MD, PhD: Lisa, you bring up a fair point as well. For years, we focused on maximum tolerated dose, but some of these medications are biologic agents, and it’s the wrong thing. We need the maximal biologic efficacy dose, not the maximum tolerated dose.

Lisa A. Carey, MD, FASCO: I totally agree with that.

Reshma Mahtani, DO: Yes. A lot of these patients were utilizing data in terms of dosing from clinical trials where patients are highly selected, highly monitored, and don’t always reflect the real-world patients you see in the clinic. I think it comes back to the idea of individualizing treatment.

Lisa A. Carey, MD, FASCO: This brings us to our next section, which is another big advance that our patients love: subcutaneous [sub-Q] formulations. Reshma, I know you have experience with these, please talk to us a bit about the combination drugs and the subcutaneous administration. The FeDeriCa and PHranceSCa trials have transformed the way we treat patients.

Reshma Mahtani, DO: We’re fortunate to have this sub-Q formulation of trastuzumab and pertuzumab as another option for patients. The FeDeriCa trial was designed to look at the pharmacokinetics, efficacy, and safety of this fixed-dose subcutaneous formulation compared to IV [intravenous] pertuzumab plus trastuzumab in patients with HER2+ disease in the neoadjuvant setting. In this trial, patients were stratified by hormone receptor status, clinical stage, and chemotherapy regimen. The primary end point was noninferiority of the cycle 7 pertuzumab serum trough concentration within the fixed-dose combination for sub-Q vs IV, and the study met its primary end point. Now we have the availability of using this sub-Q formulation, and in my practice, it’s been helpful for patients who continue HP [trastuzumab, pertuzumab] in the adjuvant setting, per the APHINITY trial data, once they are finished with the IV portion of the chemotherapy.

Many of these patients want to have their port removed. It’s a long year to be on these therapies. It is quicker to get in and out of the office with a sub-Q injection compared to the time it takes to wait for the infusion chair. We don’t need to do laboratory work before, but there still is a whole process involved with coming in for IV treatment, which I think as physicians we don’t fully recognize. We think it’s a 30-minute infusion, but patients aren’t in the office or in the chemotherapy unit for 30 minutes. A shot is a lot quicker.

The PHranceSCa trial, getting back to something we talked about earlier, which is patient preference, hearing their voice, and understanding that, in this study, there was a clear call from patients that they prefer this sub-Q formulation. I’m interested to hear from all of you if any of you have been successful in getting this administered at home. I must tell you that I’ve tried it multiple times, and I won’t pretend to understand what the hurdles are. I’ve been successful in getting patients to receive this therapy in the office, but it’s been a very difficult process for home.

Lisa A. Carey, MD, FASCO: Lee? V.K.? We haven’t. Patients still have to stay in the infusion center to get it at my institution, the UNC Lineberger Comprehensive Cancer Center.

Lee S. Schwartzberg, MD, FACP: I think there are both benefits and potential concerns for home infusion. Who’s monitoring these patients? But especially today, in our year of COVID-19, patients haven’t wanted to come into the clinic, and it’s certainly easier for them to not make a trip, particularly when they live a long distance away or it’s difficult to come in. I think we’re at the beginning of a new era. I’ve had the same experience as Reshma. It’s difficult to coordinate. But I love the idea of having subcutaneous therapy for patients not only in the adjuvant setting, but as we think about it, as our maintenance therapy, particularly in the first or second line, where these patients can be on maintenance anti-HER2 therapy with trastuzumab plus pertuzumab for months to years. To come in every 3 weeks for that and get an infusion is difficult.

A quick anecdote: I saw a patient yesterday, a 32-year-old who presented with a solitary oligometastasis in the bone, as well as her breast disease. We treated her for “cure,” and she had a pCR [pathologic complete response]in the breast tissue and on PET [positron emission tomography] scan. We radiated the 1 bone lesion, and she is on trastuzumab plus pertuzumab, and she wants to live her life. By the way, she was 12 months postpartum upon diagnosis, so she doesn’t want to come in every 3 weeks and get IVs. We switched her to subcutaneous, and I told her, “We’re going to stay on this indefinitely, but this is a lot easier for you.” That’s a great example of this.

Lisa A. Carey, MD, FASCO: But not at home.

Lee S. Schwartzberg, MD, FACP: Not at home yet.

Vijayakrishna Gadi, MD, PhD: Likewise, I haven’t been successful with the home thing, but I think that might be—we’re all advocating for home usage—and that might be a barrier that falls, hopefully. Lee, I’ll share one anecdote. I had a similar patient, a young woman who was pregnant during her breast cancer diagnosis. She got through the pregnancy, and when it came time for me to give her the subcutaneous therapy, she declined. She’s my only patient to ever decline, and her reasoning was that treatment was the only time she got to herself.

Lee S. Schwartzberg, MD, FACP: So the infusion center can be a positive, V.K.

Lisa A. Carey, MD, FASCO: Listen, the patient preference study didn’t say 100% preferred it. That is funny.

Reshma Mahtani, DO: As we’re bringing up anecdotes, I’ll say that I think all of us in our practices have a few patients in the metastatic setting who have been exquisite responders to therapy, and have been on years of treatment with either single-agent trastuzumab, or more recently, the trastuzumab, pertuzumab combination, just dual-antibody therapy. This offers them the option to get in and out of the infusion suite very quickly.

Transcript Edited for Clarity