Efficacy and safety of inetetamab plus pertuzumab and nab-paclitaxel as neoadjuvant therapy for HER2+ breast cancer: A single-arm multicenter phase II clinical trial.

The combination of inetetamab and vinorelbine has demonstrated survival benefits with an acceptable toxicity profile in HER2+ metastatic breast cancer (MBC) patients. This multicenter, single-arm, phase II trial further evaluates the efficacy of inetetamab combined with pertuzumab and nab-paclitaxel as neoadjuvant therapy. Treatment-naïve patients with HER2+ early-stage or locally advanced BC received four cycles of intravenous inetetamab (8 mg/kg loading dose, then 6 mg/kg for subsequent doses), intravenous pertuzumab (840 mg loading dose, then 420 mg for subsequent doses), and weekly nab-paclitaxel (125 mg/m). The primary endpoint was the total pathological complete response (tpCR) rate, defined as ypT0/is and ypN0, assessed by independent central review. From March 2023 to February 2024, 62 patients were enrolled, with the majority (61/62) completing 4 cycles of neoadjuvant therapy. The tpCR rate was 56.5 % (95 % CI: 43.3 %-69.0 %). Further analysis showed that patients with estrogen receptor (ER) negative tumors derived greater benefit, with a tpCR rate of 90.9 %. The objective response rate was 90.3 % (95 % CI: 80.1 %-96.4 %). The most common grade 3 or higher adverse events were neutropenia (32.3 %), decreased white blood cell count (19.4 %), infectious pneumonia (3.2 %), anemia (3.2 %), and diarrhea (3.2 %). No death occurred during the neoadjuvant treatment. Neoadjuvant treatment with inetetamab, in combination with pertuzumab and nab-paclitaxel, demonstrates good efficacy and tolerability, especially in ER-negative patients.