Neoadjuvant Inetetamab Plus Pyrotinib Phase II Trial for HER2-Positive Breast Cancer

This prospective multicenter single-arm phase II trial enrolled treatment-naive patients with stage II-III HER2-positive breast cancer to receive six cycles of neoadjuvant chemotherapy combined with the HER2-directed macromolecular agent Inetetamab and the tyrosine kinase inhibitor Pyrotinib. Between November 27, 2021, and December 18, 2025, 140 patients were enrolled, of whom 117 were evaluable for efficacy. The total pathologic complete response (tpCR; ypT0/is ypN0) rate was 61.5% (72/117; 95% CI, 52.6–70.5). The tpCR rate was significantly higher in hormone receptor (HR)-negative versus HR-positive tumors (76.2% vs 44.4%; odds ratio 0.25; 95% CI, 0.11–0.55; P < 0.001). The most common adverse events were anemia (89.2%), diarrhea (82.4%), and hypokalemia (47.3%), with grade ≥ 3 events including anemia, diarrhea, and leukopenia; no treatment-related deaths occurred. Neoadjuvant Inetetamab plus Pyrotinib with chemotherapy demonstrated clinically meaningful antitumor activity and a manageable safety profile in this population, supporting further randomized trials.