The phase III FeDeriCa trial found that a fixed-dose subcutaneous injection of pertuzumab and trastuzumab with hyaluronidase in combination with intravenous chemotherapy was pharmacokinetically noninferior to the standard IV infusions of the regimen in patients with HER2-positive breast cancer.<br />
Sandra Horning, MD
The phase III FeDeriCa trial (NCT03493854) found that a fixed-dose subcutaneous injection of pertuzumab (Perjeta) and trastuzumab (Herceptin) with hyaluronidase in combination with intravenous (IV) chemotherapy was pharmacokinetically noninferior to the standard IV infusions of the regimen in patients with HER2-positive breast cancer.1
The safety profile of pertuzumab and trastuzumab at the fixed dose was consistent with that of pertuzumab and trastuzumab when administered intravenously, and the primary endpoint for the trial was also met. Full findings from the phase III FeDeriCa study will be presented at an upcoming medical meeting, as well as submitted to international health authorities, including the FDA, Genentech (Roche), the company that develops pertuzumab and trastuzumab, stated in a press release.
“With this single injection under the skin, people with HER2-positive breast cancer receiving Perjeta and Herceptin can have a faster treatment option,” Sandra Horning, MD, chief medical officer and head of Global Product Development, said in the press release. “Our medicines have helped millions of people living with HER2-positive breast cancer and this latest development is particularly exciting as, for the first time, we have combined 2 therapeutic antibodies as a single subcutaneous formulation.”
Subcutaneous administration of the fixed-dose combination takes approximately 8 minutes for the initial loading dose, and about 5 minutes for each subsequent maintenance dose. This is in comparison to approximately 150 minutes for infusion of a loading dose of pertuzumab and trastuzumab using the standard IV formulations, and between 60 and 150 minutes for subsequent maintenance infusions for the combination.
In the international, multicenter, 2-arm, randomized, open-label, phase III FeDeriCa study, investigators evaluated the pharmacokinetics, efficacy and safety of subcutaneous injection of the fixed-dose combination of pertuzumab and trastuzumab in combination with chemotherapy versus standard IV infusion of pertuzumab/trastuzumab plus chemotherapy in approximately 500 patients with HER2-positive early breast cancer who are receiving treatment in the neoadjuvant and adjuvant settings.
To be eligible for enrollment, patients had an ECOG performance status ≤1; have stage II to IIIC locally advanced, inflammatory, or early-stage unilateral and histologically confirmed invasive breast cancer; primary tumor >2 cm in diameter or node-positive disease; and hormone receptor status of the primary tumor that is centrally confirmed. Those with stage IV metastatic disease, a history of invasive breast cancer, had received prior systemic therapy, and had axillary lymph node dissection prior to start of neoadjuvant therapy, among other criteria, were excluded from enrollment.
Patients received 8 cycles of investigator's choice of neoadjuvant chemotherapy, which could include 4 cycles of dose-dense doxorubicin plus cyclophosphamide every 2 weeks, followed by weekly paclitaxel for 12 weeks; or 4 cycles of doxorubicin plus cyclophosphamide once every 3 weeks followed by docetaxel every 3 weeks for 4 cycles. Pertuzumab and trastuzumab were given IV or subcutaneously for 4 cycles every 3 weeks concurrently with the taxane portion of the chemotherapy. After completing their neoadjuvant therapy, patients underwent surgery. Patients then received an additional 14 cycles of either pertuzumab IV and trastuzumab IV or fixed-dose pertuzumab/trastuzumab for a total of 18 cycles.
The primary endpoint of the study is Ctrough of pertuzumab in the blood during a given dosing interval; secondary endpoints include safety, Ctrough of trastuzumab in the blood during a given dosing interval, and total pathologic complete response.
In February 2019, the FDA approved subcutaneous use of trastuzumab and hyaluronidase-oysk injection (Herceptin Hylecta) in combination with chemotherapy for the treatment of select patients with HER2-positive early breast cancer, in combination with paclitaxel in patients with metastatic HER2-positive breast cancer as a frontline treatment, and alone for patients with metastatic disease who have received ≥1 prior chemotherapy regimen.2
The approval was based on findings from the HannaH (NCT00950300) and SafeHER (NCT01566721) studies, in which Herceptin Hylecta demonstrated comparable rates of efficacy and safety compared with the standard IV use of trastuzumab, as well as the PrefHER trial (NCT01401166), which suggested a patient preference for the subcutaneous regimen.