The randomized, open-label, phase 3 FeDeriCa trial tested the safety profile of pertuzumab and trastuzumab plus hyaluronidase-zzxf in 500 patients with HER2-positive early breast cancer.
Research examining the pertuzumab (Perjeta) and trastuzumab (Herceptin) combination formulated with hyaluronidase-zzxf (Phesgo) for subcutaneous injection demonstrated noninferiority versus intravenous pertuzumab plus trastuzumab in the neoadjuvant setting for patients with HER2-positive early breast cancer based on cycle 7 pertuzumab serum trough concentrations, according to data published in The Lancet.
The data from the phase 3 FeDeriCa trial (NCT03493854) met its primary end point, showing a comparable total pathological complete response rate while also producing a similar safety profile with that of the intravenous formulation. These data also compare favorably with other trials investigating pertuzumab, trastuzumab, and chemotherapy for patients with HER2-positive early breast cancer and further support the drug’s FDA approval.
“Overall, the efficacy and safety data for the fixed-dose combination plus chemotherapy from this study were consistent with the known efficacy and safety profile of pertuzumab plus trastuzumab plus chemotherapy in patients with HER2-positive breast cancer,” wrote the investigators who were led by Antoinette R. Tan, MD.
Patients were randomly assigned to 2 groups between June 14 and December 24, 2018, with 252 patients administered the intravenous infusion and 248 given the fixed-dose combination.
The investigators measured the geometric mean ratio of serum trough concentrations for pertuzumab subcutaneous versus intravenous at 1.22 (90% CI 1.14-1.31).
Common grade 3/4 adverse events (AEs) included neutropenia (13% of the intravenous infusion group vs 14% of the fixed-dose group), decreased neutrophil count (12% vs 11%), febrile neutropenia (6% vs 6%), diarrhea (5% vs 7%), and decreased white blood cell count (7% vs 4%).
There were treatment-related serious AEs in 10% of patients from both groups, with each group have 1 AE leading to death, although neither were related to HER2-targeted therapy.
“The results of this study add to the current knowledge regarding the subcutaneous delivery of monoclonal antibodies in oncology by confirming that the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection provides noninferior serum trough concentrations to intravenous pertuzumab plus trastuzumab in the neoadjuvant setting, with comparable total pathological complete response rates and a comparable safety profile,” wrote the investigators.
The safety population for the research included patients who received at least 1 dose of study medication, including chemotherapy or HER2-targeted therapy. While enrollment, neoadjuvant therapy, and surgery have all been completed, adjuvant treatment and follow-up are currently ongoing.
Safety, efficacy, and pharmacokinetic results are not yet available according to the investigators because the standard of care requires HER2-targeted treatment to continue for up to 18 cycles. The team expects the long-term safety and efficacy data for the fixed-dose combination to be similar to the safety and efficacy profile of the intravenous infusions.
“Overall, the evidence shows that subcutaneous administration of monoclonal antibodies offers a faster, more convenient, and less invasive treatment option for HER2-positive breast cancer than do intravenous infusions,” the investigators concluded.
Tan AR, Im SA, Mattar A, et al. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet. 2021;22(1):85-97. doi: 10.1016/ S1470-2045(20)30536-2.