Real-world outcomes and safety of inetetamab plus pyrotinib and chemotherapy in HER2-positive metastatic breast cancer: A multicenter retrospective study.

BACKGROUND: Inetetamab and pyrotinib have shown promising activity in HER2-positive metastatic breast cancer (MBC). However, real-world data on their combination with chemotherapy (IPyC) across different treatment lines remain limited. OBJECTIVES: This multicenter retrospective study aimed to describe the outcomes associated with a dual HER2-targeting strategy IPyC in HER2-positive MBC across treatment lines in real-world clinical practice. DESIGN: Multicenter retrospective study. METHODS: Between July 2020 and August 2024, 301 patients with HER2-positive MBC from five tertiary centers in China received IPyC until disease progression or unacceptable toxicity. Key outcome measures included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Cox proportional hazards models were used to identify potential prognostic factors. RESULTS: The median IPyC associated PFS and OS for the entire cohort were 12.0 months (95% CI: 10-15) and 33.0 months (95% CI: 28-42), respectively, with an ORR of 50.2% and a CBR of 80.4%. The IPyC associated PFS varied significantly by treatment line (23.0, 17.0, and 6.0 months for first-line, second-line, and ≥third-line, respectively; p<0.001). In first-line setting, baseline lymphovascular invasion (LVI) and multiple metastases were independent prognostic factors, and trastuzumab-naïve patients had a numerically longer median PFS of 27.0 months than those with prior trastuzumab exposure. In second-line setting, patients with secondary resistance to trastuzumab achieved a median PFS of 24.0 months. A new central nervous system (CNS) metastasis incidence was observed in 6.6% (5/76) of patients without baseline CNS metastases in the first-line IPyC treatment setting. The IPyC regimen was associated with manageable toxicity, with grade 3-4 diarrhea (26.2%), neutropenia (16.6%), and leukopenia (12.6%) as the most common adverse events (AEs). CONCLUSION: As a retrospective descriptive study, our analysis describes the use and outcomes of the IPyC regimen across multiple lines of therapy in HER2-positive MBC, highlighting the need for and supporting the design of prospective studies to evaluate this regimen.