Pertuzumab and Trastuzumab: Patient Eligibility, Administration Methods, and Dosing Strategies


Clinical insights concerning the administration of combination pertuzumab/trastuzumab/hyaluronidase-zzxf for patients with HER2-positive breast cancer.

Joyce O’Shaughnessy, MD: We have available now for patients, a new formulation of trastuzumab and pertuzumab, and that's a subcutaneous formulation that is mixed with hyaluronidase to help the tissue penetration of the antibodies when it's given subcutaneously. This is a very nice option for patients because it allows them, for example, not to receive IV trastuzumab and pertuzumab. It saves them time and also over time, they may even be able to discontinue the portacath, just have it removed. That's very nice for patients and the subcutaneous, trastuzumab, and pertuzumab is indicated by the FDA for each of the indications where we currently use IV trastuzumab and pertuzumab. That is preoperatively or in the adjuvant setting or in the first line metastatic setting. That's where we use the combination and that's where we're now able to offer patients as subcutaneous trastuzumab and pertuzumab as well.

Subcutaneous trastuzumab and pertuzumab can be used both in the curative setting as well as in the metastatic setting. It's basically administered exactly how you would administer IV trastuzumab and pertuzumab. It can be given subcutaneously preoperatively with chemotherapy, for patients who are presenting with stage two or three HER2-positive breast cancer. It's given preoperatively along with chemotherapy then the patients go to surgery. If they're a pathologic complete response, then they can continue the trastuzumab and pertuzumab subcutaneously to finish up that standard year of the combined antibody therapy with endocrine therapy in the adjuvant setting, if they're hormone receptor-positive. If the patients have residual disease at surgery, then they're finished with the trastuzumab and pertuzumab and they go onto the T-DM1 for 10 months. That's in the curative setting. In the metastatic setting in the first-line setting in combination with a taxane, paclitaxel or docetaxel, we can give the subcutaneous trastuzumab and pertuzumab. Their patients remain on the trastuzumab and pertuzumab for as long as they are without disease progression. Generally, for some patients, this is many years and for some, it's a lifelong therapy, and it's very nice to obviously have the subcutaneous version for these patients who will be on trastuzumab and pertuzumab for many years.

When patients are first begun on trastuzumab and pertuzumab for their very first dose IV, we give a loading dose of both pertuzumab and trastuzumab for the first dose, and then every three weeks thereafter, they receive the maintenance dose of IV trastuzumab and pertuzumab. When patients are receiving subcutaneous trastuzumab and pertuzumab, the first dose involves a loading dose of the pertuzumab in the syringe, along with the trastuzumab. Then after the first dose, they receive the maintenance dose of the trastuzumab and the pertuzumab subcutaneously. I'll just stop here for one second. Let him finish up here. He's OK. For patients who have been receiving IV trastuzumab and pertuzumab, they're already at steady state with their dosing regimen and so when you switch them over to subcutaneous trastuzumab and pertuzumab, generally for their convenience, you don't need a loading dose of the trastuzumab and pertuzumab. You just give the maintenance dosing which is 600 milligrams of the pertuzumab and 600 milligrams of the trastuzumab. You're just continuing therapy at that point. There's really no issue with switching a patient from the IV to the subcutaneous. It's really very seamless. Instead of getting IV, they go ahead and get a subcutaneous dosing. There's very well tolerated. There's no issues with toxicity and they don't need a loading dose because they're already at steady state with the trastuzumab and pertuzumab in their plasma.

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