Real-world outcomes and safety of inetetamab plus pyrotinib and chemotherapy in HER2-positive metastatic breast cancer: A multicenter retrospective study
Fan Wu, Cailing Lin, Zhiwu Lin, Qingmo Yang, Xiuping Wu, Biyin Chen, Nani Li, Ruxue Zhang, Xiufeng Wu, Weiwei Huang, Xinhua Chen, Yi Hong, Kan Chen, Jian LiuBackground
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.