Pyrotinib combined with trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer: a single-arm exploratory phase II trial.

Abstract

PURPOSE:

A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC.

METHODS:

In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety.

RESULTS:

Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI] 4.7 to 9.9 months) and 9.4 months (95% CI 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed.

CONCLUSION:

Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases.

• Authors: Xiao-Feng Xie, Qiu-Yi Zhang, Jia-Yi Huang, Li-Ping Chen, Xiao-Feng Lan, Xue Bai, Lin Song, Shui-Ling Xiong, Si-Jia Guo, Cai-Wen Du
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 197 Issue 1 Pg. 93-101 (Jan 2023) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 36309908 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Trastuzumab
• ERBB2 protein, human
• pyrotinib
• Receptor, ErbB-2

Topics

• Humans
• Female
• Trastuzumab
• Breast Neoplasms (pathology)
• Receptor, ErbB-2 (metabolism)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)