FDA Approval Insights: Fixed-Dose Pertuzumab/Trastuzumab in HER2+ Breast Cancer

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Jessica Hergert.

OncLive^® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Antoinette R. Tan, MD, chief of Breast Medical Oncology and co-director of the Phase I Program at the Levine Cancer Institute of Atrium Health, to discuss the FDA approval of the fixed-dose combination of pertuzumab (Perjeta) and trastuzumab (Herceptin) with hyaluronidase-zzxf (Phesgo) for administration via subcutaneous injection in combination with intravenous (IV) chemotherapy, for patients with early and metastatic HER2-positive breast cancer.

The June 29, 2020 approval marks the first time that Genentech, the drug developer, has combined 2 monoclonal antibodies that can be administered via a single subcutaneous injection. Patients should be selected for this combination based on an FDA-approved companion diagnostic test.

The combination is available in 1 single-dose vial. The initial loading dose is estimated to take approximately 6 minutes to administer with each subsequent maintenance dose taking approximately 5 minutes. Typically, infusion of a loading dose of the standard IV formulations of pertuzumab and trastuzumab take approximately 150 minutes; subsequent maintenance infusions of the 2 agents can take anywhere from 60 to 150 minutes. The newly approved combination allows for administration by a healthcare professional in either a treatment center or at home.

The regulatory decision was based on findings from the phase 3 FeDeriCa trial, in which the combination demonstrated noninferiority to IV formulations of the 2 drugs with regard to pharmacokinetics, clinical efficacy, and safety.

The study enrolled a total of 500 patients and met its primary end point after showing noninferiority on the basis of predose cycle 8 serum Ctrough for the pertuzumab component of the fixed-dose combination.

Additionally, results from the trial showed noninferiority for the predose cycle 8 serum Ctrough for the trastuzumab component of the fixed-dose combination versus with IV trastuzumab.

Notably, total pathologic complete response in the breast and axilla, as well as safety, was found to be comparable between the 2 treatment regimens.

With regard to safety, the most common adverse events observed with the combination include alopecia, nausea, diarrhea, anemia, and asthenia. The combination can also lead to the worsening of chemotherapy-induced neutropenia, according to the FDA.

Notably, prescribing information for the combination includes a boxed warning to health care professionals and patients about the risk of potential heart failure, fetal harm, and lung events. Providers should use similar monitoring parameters as those used with IV pertuzumab and IV trastuzumab.

In our exclusive interview, Tan discussed the FDA approval of the fixed-dose combination and highlighted the results of the pivotal FeDeriCa trial.