FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase–zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer

Abstract

On June 29, 2020, the FDA approved pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (Phesgo) for the treatment of patients with HER2-positive early stage and metastatic breast cancer. Patients should be selected for therapy based on an FDA-approved companion diagnostic test. Approval was primarily based on the FeDeriCa trial, a randomized, open-label, multi-center comparability study of pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection compared to intravenous (IV) pertuzumab and IV trastuzumab administered in the neoadjuvant and adjuvant settings with chemotherapy for the treatment of patients with early breast cancer. The pharmacokinetic endpoints were, first, to demonstrate that the exposure of subcutaneous pertuzumab was not inferior to that of IV pertuzumab, and then to demonstrate that the exposure of subcutaneous trastuzumab was not inferior to that of IV trastuzumab. The primary endpoints were met, with the observed lower limit of the two-sided 90% confidence intervals above the pre‑specified non-inferiority margins. The most common adverse reactions were alopecia, nausea, diarrhea, anemia, and asthenia. The totality of the evidence demonstrated comparability of the subcutaneous product to IV, allowing for extrapolation and approval of all breast cancer indications for which IV trastuzumab and pertuzumab are approved.