medwireNews: Subcutaneous administration of pertuzumab and trastuzumab generates similar pertuzumab serum trough concentrations (Ctrough) to those seen with intravenous pertuzumab plus trastuzumab in women with HER2-positive breast cancer, research shows.
The two neoadjuvant treatment delivery methods also resulted in comparable pathologic complete response (pCR) rates and safety profiles among participants of the phase 3 FeDeriCa trial, report Antoinette Tan (Atrium Health, Charlotte, North Carolina, USA) and co-investigators in The Lancet Oncology.
As previously reported by medwireNews, the subcutaneous formulation of pertuzumab and trastuzumab with recombinant human hyaluronidase (pertuzumab, trastuzumab, and hyaluronidase-zzxf), supplied in a ready-to-use, fixed-dose combination vial, was approved by the US FDA in June 2020.
The current international study assessed its pharmacokinetics, efficacy, and safety relative to intravenous pertuzumab plus trastuzumab, each in combination with chemotherapy, in 500 patients with HER2-positive operable, locally advanced, or inflammatory stage II–IIIC breast cancer in the neoadjuvant–adjuvant setting.
Tan and team found that the primary endpoint of geometric mean cycle 7 pertuzumab serum Ctrough was 88.7 µg/mL in the 252 patients randomly assigned to receive subcutaneous treatment (1200 mg pertuzumab plus 600 mg trastuzumab loading dose in 15 mL, followed by 600 mg pertuzumab plus 600 mg trastuzumab maintenance doses in 10 mL) every 3 weeks.
By comparison, the geometric mean cycle 7 pertuzumab serum Ctrough was 72.4 µg/mL in the 248 patients given 3-weekly intravenous pertuzumab (840 mg loading dose, followed by 420 mg maintenance doses) plus trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg maintenance doses).
The resulting geometric mean ratio (GMR) of the subcutaneous to intravenous pertuzumab Ctrough was 1.22, with the lower limit of the two-sided 90% confidence interval above the prespecified noninferiority margin of 0.80.
The GMR of cycle 7 trastuzumab serum Ctrough was 1.33 and also showed noninferiority between the two treatment delivery methods.
In their hypothesis, the researchers suggested that “a non-inferior Ctrough would ensure at least the same degree of target saturation as with intravenous administration, ensuring similar efficacy.”
The pCR rates mirrored this suggestion, at 59.7% and 59.5% with subcutaneous and intravenous treatment, respectively.
The researchers also report that safety was “similar between treatment groups, and in line with other pertuzumab, trastuzumab, and chemotherapy trials.”
Serious adverse events occurred in 10% of patients in each treatment group and one patient in each group had an adverse event unrelated to HER2-targeted therapy that led to death (acute myocardial infarction in the subcutaneous group and urosepsis in the intravenous infusion group).
Tan et al conclude: “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.”
They add: “Follow-up is ongoing for long-term outcomes, including efficacy and long-term safety.”
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