December 23, 2020 - The European Commission has approved the fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase, to be administered via a subcutaneous injection in the treatment of patients with early and metastatic HER2-positive breast cancer.
The European Commission has approved the fixed-dose combination of pertuzumab (Perjeta) and trastuzumab (Herceptin) with hyaluronidase (Phesgo), to be administered via a subcutaneous injection in the treatment of patients with early and metastatic HER2-positive breast cancer.1
The regulatory decision is based on data from the phase 3 FeDeriCa trial (NCT03493854), which demonstrated that the fixed-dose regimen resulted in noninferior levels of pertuzumab and trastuzumab in the blood, while showcasing similar efficacy compared with the IV regimen.2
“This approval represents a significant step forward in the treatment of HER2-positive breast cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “The innovation of Phesgo significantly reduces the time people spend receiving standard-of-care therapy with [pertuzumab] and [trastuzumab], helping to minimize the impact of treatment on their everyday lives. It also addresses the increasing demand across healthcare systems for faster and more flexible treatment solutions.”
The single-dose vial for subcutaneous delivery allows for over 90% faster treatment than that of the intravenous (IV) administration of pertuzumab/trastuzumab. The fixed-dose regimen requires just 8 minutes to deliver the initial loading dose and about 5 minutes for each subsequent dose; the IV infusion requires about 150 minutes for the initial loading dose and anywhere from 60 minutes to 150 minutes for the subsequent maintenance doses of the 2 agents.
The international, multicenter, open-label, phase 3 FeDeriCa trial enrolled a total of 500 participants. The trial was reported to have met its primary end point after noninferiority was established based on predose cycle 8 serum Ctrough for the pertuzumab component of the regimen; the mean value was 93.7 µg/mL compared with 75 µg/mL for IV pertuzumab. Moreover, geometric means for the subcutaneous and IV formulations were 88.7 µg/mL vs 72.4 µg/mL, respectively (geometric mean ratio [GMR], 1.22; 90% CI, 1.14-1.31).
Additional findings demonstrated noninferiority for the trastuzumab component of the regimen, as well; the mean values for the subcutaneous and IV formulations were 62.9 µg/mL compared with 48.1 µg/mL, respectively, and the geometric means were 58.7 µg/mL and 44.1 µg/mL, respectively (GMR, 1.33; 90%, CI, 1.24-1.43).
Notably, the total pathologic complete response (tpCR) in both the breast and the axilla was found to be comparable between the 2 approaches, as were the safety data.
Previously, in the phase 1b dose-finding trial, referred to as HannaH, investigators had identified the recommended dose for both trastuzumab and hyaluronidase-oysk (Herceptin Hylecta).3 The recommended dose of pertuzumab had been determined in another phase 1b dose-finding trial.4
The subcutaneous, fixed-dose regimen had been evaluated as a neoadjuvant treatment in patients with newly diagnosed stage II-IIIC HER2-positive breast cancer who had been enrolled to a total of 122 clinical sites. The median age of patients was 50 years and more than half of patients, or 61%, had hormone receptor–positive disease. Moreover, 80% of patients had stage II-IIIA disease.
In the trial, participants received either 4 cycles of chemotherapy comprised of doxorubicin and cyclophosphamide followed by 4 cycles of docetaxel administered with randomized therapy of either IV pertuzumab/trastuzumab or the fixed-dose subcutaneous regimen.
Following surgery, participants were given adjuvant treatment with the same regimen that they had received in the neoadjuvant setting. Investigators conducted the primary analysis of the research prior to the initiation of adjuvant treatment.
Results indicated that the GMRs fell within the 90% confidence intervals for noninferiority. Moreover, the tpCR rates observed with the 2 treatment approaches were nearly identical. Specifically, the tpCR elicited with the subcutaneous and IV formulations were 59.7% and 59.5%, respectively.
In terms of safety, the most common adverse effects reported with the regimen included alopecia, nausea, diarrhea, anemia, and asthenia; the combination can also potentially lead to worsening of chemotherapy-induced neutropenia.
In June 2020, the FDA had approved the fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase-zzxf for subcutaneous administration in combination with IV chemotherapy in patients with early and metastatic HER2-positive breast cancer.