Efficacy and safety of the pertuzumab biosimilar BCD-178 versus the originator pertuzumab in patients with HER2-positive locally advanced breast cancer: Results from the international, double-blind, randomized, phase III PREFER trial.

613 Background: Pertuzumab, a HER2-targeting monoclonal antibody, significantly improves outcomes for patients with HER2-positive breast cancer (HER2+ BC) in different settings in combination with another HER2-agents with/without chemotherapy. BCD-178 is a biosimilar of the originator pertuzumab (OP). Preclinical and phase I clinical studies have demonstrated its equivalence to OP. The phase III PREFER trial compared the efficacy and safety of BCD-178 and OP as neoadjuvant and adjuvant therapy in HER2+ BC. Methods: The study hypothesized that neoadjuvant therapy containing BCD-178 would yield a pathological complete response (pCR) rate equivalent to that of therapy containing OP in women aged 18–75 years with stage II–III HER2+, hormone receptor-negative invasive BC and a primary tumor > 2 cm. Patients were randomized 1:1 to receive neoadjuvant therapy with either BCD-178 or OP, combined with trastuzumab and chemotherapy (TCHP regimen). The primary endpoint was the pCR rate (ypT0/is, ypN0) assessed by central independent review. Safety was monitored throughout, with adverse events (AEs) graded by CTCAE v5.0. Immunogenicity and pharmacokinetics were also evaluated (NCT05802225). Results: Of 398 randomized patients, 201 received BCD-178 and 197 received OP. The median age was 53 years; over one-third of patients in each group had stage IIIB/IIIC disease. pCR rates were 75.0% with BCD-178 and 72.2% with OP (risk ratio RR 2.7, 95% CI: -6.0 to 11.6). The 95% CI for the between-group difference in pCR rate fell within the predefined equivalence margins, confirming equivalent efficacy. The safety profiles were comparable. The most common AEs (≥10%) were diarrhea and anemia. Immunogenicity was low and similar between groups: binding antibodies were detected in 1.6% (BCD-178) vs. 1.1% (OP) of patients, and neutralizing antibodies in 1.1% in both groups. The concentration-time profiles and pharmacokinetic profiles (Cmin, Ceoi) were also comparable. Conclusions: In patients with HER2+, hormone receptor-negative locally advanced breast cancer, the biosimilar BCD-178 demonstrated equivalent efficacy, safety, immunogenicity, and pharmacokinetics to the originator pertuzumab within a neoadjuvant TCHP regimen. Clinical trial information: NCT05802225 .