Fixed Combination of Trastuzumab and Pertuzumab for Subcutaneous Administration in Patients with Early Breast Cancer

Combined treatment of breast cancer

Adding pertuzumab to trastuzumab and chemotherapy improves therapeutic outcomes in patients with HER2-positive breast cancer. The drugs are usually administered in the form of an infusion, which takes approximately 60–150 minutes.

The new fixed-dose combination for subcutaneous administration contains both antibodies as well as recombinant human hyaluronidase in one dose, which temporarily breaks down hyaluronan in the tissue, aiding the dispersion and absorption of the drugs after subcutaneous application. In the presented study, the drug was administered as a subcutaneous injection into the thigh over 5–8 minutes.

Study methodology

The phase III multicenter open-label study involved 500 patients with centrally confirmed HER2-positive invasive breast cancer. Patients were treated in a neoadjuvant regimen with 8 cycles of chemotherapy combined with trastuzumab and pertuzumab. The antibodies were administered intravenously (trastuzumab at an initial dose of 8 mg/kg followed by 6 mg/kg, pertuzumab at an initial dose of 840 mg followed by 420 mg) or subcutaneously as a fixed-dose combination (initial dose 600 mg trastuzumab/1200 mg pertuzumab followed by 600 mg each). After tumor resection, patients continued in anti-HER2 therapy for up to 18 cycles.

The primary goal of the study was the noninferiority of the serum concentration measured as C_trough of subcutaneously administered pertuzumab before cycle 8 compared to intravenous administration. Secondary goals included noninferiority of the serum concentration measured as C_trough of trastuzumab, the frequency of total pathological complete response of the tumor in the breast and axilla, and the safety profile (particularly concerning cardiac risk).

Results

Noninferiority of the serum concentrations C_trough of both antibodies was demonstrated for subcutaneous administration compared to intravenous administration. A total of 59.5% of patients (95% confidence interval [CI] 53.2–65.6) treated intravenously achieved pathological complete response to the treatment, while in the subcutaneous administration arm it was 59.7% (95% CI 53.3–65.8), consistent with data from previously conducted clinical evaluations. The safety profile was comparable in both study arms.

Conclusion

The pharmacokinetics, efficacy, and safety profile of subcutaneously administered trastuzumab with pertuzumab are comparable to intravenous administration. The fixed-dose combination of antibodies for subcutaneous administration thus represents a simpler and faster alternative for treating HER2-positive breast cancer.

(este)

Sources:
1. Tan A. R., Im S.-A., Mattar A., et al. Subcutaneous administration of the fixed-dose combination of trastuzumab and pertuzumab in combination with chemotherapy in HER2-positive early breast cancer: primary analysis of the phase III, multicenter, randomized, open-label, two-arm FeDeriCa study. Cancer Res 2020; 80 (4 Suppl.): PD4-07. Available at: https://cancerres.aacrjournals.org/content/80/4_Supplement/PD4-07
2. FDA accepts Roche’s Biologics license application for fixed-dose subcutaneous combination of Perjeta and Herceptin for HER2-positive breast cancer. Press release. F. Hoffmann-La Roche, 2020 Feb 25. Available at: www.globenewswire.com/news-release/2020/02/25/1989665/0/en/FDA-accepts-Roche-s-Biologics-License-Application-for-fixed-dose-subcutaneous-combination-of-Perjeta-and-Herceptin-for-HER2-positive-breast-cancer.html