FDA Accepts BLA for Fixed-Dose Combination Therapy for HER2-Positive Breast Cancer
Posted: Wednesday, March 4, 2020
On February 25, the U.S. Food and Drug Administration (FDA) accepted a biologics license application (BLA) for a fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase, administered by subcutaneous (SC) injection in combination with intravenous (IV) chemotherapy for eligible patients with HER2-positive breast cancer. The monoclonal antibodies pertuzumab and trastuzumab bind to the HER2 receptor—but in different locations, thus potentially offering dual blockade of the HER signaling pathway.
SC administration of pertuzumab and trastuzumab can occur in approximately 8 minutes of the initial loading dose and 5 minutes for each subsequent maintenance dose. This schedule is compared with 150 minutes for infusion of a loading dose of pertuzumab and trastuzumab using standard IV formulations and 60 to 150 minutes for later maintenance infusions.
This approval is supported by data from the phase III FeDeriCa clinical trial. This two-arm, open-label study assessed the pharmacokinetics, efficacy, and safety of SC injections compared with standard IV infusion for this fixed-dose combination with chemotherapy. The study enrolled 500 people with HER2-positive early breast cancer who were treated in neoadjuvant and adjuvant settings.
In a given dosing interval, SC administration of the fixed-dose combination yielded noninferior levels of pertuzumab as well as trastuzumab in the blood compared with IV administration. Rates of total pathologic complete response were comparable between treatment arms. No new safety signals were identified, and the safety profile of the fixed-dose combination with chemotherapy was comparable to that of IV administration. Common adverse reactions such as alopecia, nausea, diarrhea, and anemia were noted in both treatment arms.
