Neoadjuvant intravenous biosimilar pertuzumab and trastuzumab versus subcutaneous pertuzumab/trastuzumab/hyaluronidase (Phesgo) in HER2-positive breast cancer: A real-world comparative study.

e12604 Background: Dual HER2 blockade with pertuzumab and trastuzumab combined with chemotherapy is the standard neoadjuvant treatment for HER2-positive breast cancer. In low- and middle-income countries, biosimilar pertuzumab and trastuzumab are increasingly used due to improved affordability. Phesgo, a fixed-dose subcutaneous formulation of pertuzumab and trastuzumab, offers logistical convenience. Comparative real-world data evaluating neoadjuvant outcomes between biosimilar-based intravenous dual HER2 blockade and Phesgo are limited. Methods: This retrospective observational study included patients with HER2-positive breast cancer who received neoadjuvant chemotherapy and dual HER2 blockade using either intravenous biosimilar Pertuzumab with Trastuzumab or subcutaneous fixed dose combination of Pertuzumab/Trastuzumab/Hyaluronidase i.e, Phesgo (Roche) from 01.01.2024 to 20.01.2026. Baseline demographic and clinicopathological characteristics, neoadjuvant regimens, surgical outcomes, and pathological response were analyzed. Pathological complete response (pCR) was defined as ypT0N0 or ypTisN0 among patients who underwent surgery. Results: A total of 219 patients were analyzed, of which 149 (68%) received biosimilar pertuzumab/trastuzumab and 70 (32%) received Phesgo. Median age was comparable between the groups (52 vs 53 years). Hormone receptor–positive disease was seen in 45.7% and 51.4% of patients, respectively. The majority of patients in both cohorts had T1–T2 tumors (62.4% vs 62.9%), while node-positive disease was more frequently observed in the Phesgo cohort (67.8% vs 77.1%). Neoadjuvant chemotherapy was administered in 96% of patients in both cohorts, most commonly TCHP regimen. At the time of analysis, neoadjuvant treatment was ongoing in 31 of 149 patients (20.8%) in the biosimilar group compared with 3 of 70 patients (4.3%) in the Phesgo group. Surgery was completed in 65.8% of the biosimilar group and 82.8% of the Phesgo group, with comparable breast-conserving surgery rates (33.7% vs 34.5%). Among patients with available surgical pathology data (n = 92 vs n = 56), pCR rates were similar between cohorts (ypT0N0: 64.1% vs 64.3%; ypTisN0: 2.17% vs 1.8%). No significant adverse events reported other than diarrhoea. None of them had treatment discontinuation due to cardiac toxicity. Conclusions: Neoadjuvant chemotherapy combined with biosimilar intravenous pertuzumab and trastuzumab achieved pathological response and surgical outcomes comparable to Phesgo in patients with HER2-positive breast cancer. Clinical implications: These findings support biosimilar-based dual HER2 blockade as an effective and affordable neoadjuvant strategy, particularly relevant for improving access to standard-of-care therapy in resource-constrained settings.