Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study

• Published in: Therapeutic advances in medical oncology 2022, Vol.14, p.17588359221085232-17588359221085232
• Main Authors: Hua, Yijia, Li, Wei, Jin, Nan, Cai, Dongyan, Sun, Jie, Sun, Chunxiao, Yang, Fan, Wu, Xinyu, Huang, Xiang, Wang, Biyun, Yin, Yongmei
• Format: Article
• Language: English
• Subjects: Breast cancer; Cancer therapies; Diarrhea; Epidermal growth factor; ErbB-2 protein; Inhibitor drugs; Metastases; Metastasis; Original Research; Patients; Protein-tyrosine kinase; Survival; Targeted cancer therapy; Toxicity
• ISSN: 1758-8359; 1758-8340; 1758-8359
• DOI: 10.1177/17588359221085232

Background: Tyrosine kinase inhibitors (TKIs) are effective for treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, therapies subsequent to TKI progression remain controversial, and effective treatments for TKI resistance are urgently needed. We evaluate the practice of exchange of TKIs, which involves treatment with a different TKI following prior TKI failure. Specifically, this study investigated the efficacy of pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer (NCT04899128). Methods: This real-world study included 76 patients diagnosed with HER2-positive metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression at four Chinese institutions between August 2018 and March 2020. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and toxicity profiles were reported. Results: All patients received pyrotinib-based therapy in two or later line therapy. The median PFS was 8.0 months (95% CI 5.1–10.9). OS has not reached. The ORR and CBR were 17.1% and 60.5%, respectively. The median PFS was 7.1 months (95% CI 5.633–8.567) and intracranial ORR was 42.9% in patients who had brain metastasis (n = 14). Patients who benefited from lapatinib ⩾ 6.0 months prior exhibited a longer PFS (10.6 versus 6.0 months, p = 0.034, stratified hazard ratio (HR) 0.534, 95% CI 0.293–0.975). The most common adverse effects were diarrhea (n = 34, 44.7%) and hand-foot syndrome (n = 10, 13.2%). Conclusion: Pyrotinib-based therapy has the potential to improve survival in patients with lapatinib-resistant HER2-positive metastatic breast cancer, including those with brain metastases. Pyrotinib could provide a clinically significant increase in PFS for patients who benefited from prior lapatinib.