Case 1: Subcutaneous vs Intravenous Trastuzumab/Pertuzumab


An expert in breast cancer considers the role of intravenous and fixed-dose subcutaneous formulations of trastuzumab/pertuzumab as studied in the FeDeriCa and PHranceSCa clinical trials.


Chau T. Dang, MD: We use IV [intravenous] trastuzumab-pertuzumab during the chemotherapy phase because the patient already has a needle inserted, and it’s easy to continue delivering IV trastuzumab-pertuzumab after the chemotherapy to avoid another needle stick. We’ve typically used the fixed-dose combination of subcutaneous trastuzumab-pertuzumab after the patient is done with chemotherapy, when patients are to complete the rest of the metastatic HER2 [human epidermal growth factor receptor 2] treatment, especially those who have a pathologic complete response [pCR] rate after neoadjuvant therapy treatment and continue on with trastuzumab-pertuzumab. It saves chair time to have the subcutaneous formulation, but the subcutaneous formulation can be delivered during chemotherapy too.

There are 2 data sets. One is the FeDeriCa study. This is a study that randomized patients who have clinical stage II/III HER2-positive breast cancer to IV formulation of trastuzumab-pertuzumab chemotherapy, or the fixed-dose combination of subcutaneous trastuzumab-pertuzumab in chemotherapy. The primary end point was to look for the noninferiority of the cycle 7 pertuzumab trough concentration. When comparing the subcutaneous formulation against IV formulation, it was found to have met its primary end point. Initially, it also showed that the pCR rates were the same, whether patients had the subcutaneous formulation or the IV formulation. That’s 1 study.

The second study was the PHranceSCa study, which was designed to assess patient preference for fixed-dose combination in comparison with IV formulation of trastuzumab-pertuzumab, and the majority of patients preferred the fixed-dose subcutaneous formulation of trastuzumab-pertuzumab and there were no new safety signals.

In the beginning of spring 2020, we had no idea what the significance of the COVID-19 pandemic was going to have on our patients with an immunocompromised status, so many of us made the decision to give the taxane phase of treatment. If patients were offered an anthracycline-taxane combination with NA [neoadjuvant] HER2 therapy, we’d opt to give the taxane phase first because there’s less myelosuppression during that phase, so we’d flip the sequence. We’d give the taxane phase first with antibody therapy, followed by anthracycline, but little did we know that the pandemic continued beyond several months. That was 1 slight change. The other 1 was that we started to adopt using the subcutaneous formulation of trastuzumab-pertuzumab when it was approved in June 2020, for ease of delivery and to minimize the time the patient was in the clinic. It did slightly change our practice without compromising efficacy.

For both IV formulation and subcutaneous formulation, it’s been diarrhea, with grade 3 event of less than 10%, so it’s very similar for both. We’ve learned how to manage diarrhea well with supportive medications. As far as the subcutaneous formulation goes, patients report more injection-site discomfort. It’s very predictable that patients will have diarrhea, so we educate our patients to be aware of diarrhea, hydrate, and have a loperamide at home and ready to take 2 loperamide tablets if they experienced an event and to have more as needed. Hydrate, and if they have more than grade 1 diarrhea, we ask them to report to us so we can coach them on how to further enhance their antidiarrheal regimens to basically control it. Certainly, trastuzumab-pertuzumab is relatively easy to give, with fewer diarrhea events than we’ve seen with tyrosine kinase inhibitors.

Transcript edited for clarity.

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