Intracranial Efficacy of Pyrotinib and Capecitabine Combination Therapy in HER2-Positive Breast Cancer with Brain Metastases

Abstract

Aim

Approximately 50% of patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC) are estimated to develop brain metastases (BMs). This study was aimed to assess the intracranial efficacy and survival benefits of pyrotinib and capecitabine combination therapy in the treatment of BMs in patients with HER2-positive BC.

Methods

A total of 56 HER2-positive BC patients with BMs were treated with 400 mg pyrotinib once daily along with 1000 mg/m² capecitabine twice daily for 14 days in 21-day cycles. The patients were allocated into three cohorts: (1) Cohort A composed of patients with newly diagnosed BMs without prior local radiotherapy, (2) Cohort B included patients with stable post-local radiotherapy, and (3) Cohort C composed of patients with progression following local radiotherapy. The primary endpoint was the intracranial objective response rate (CNS-ORR), while secondary endpoints included intracranial disease control rate (CNS-DCR), progression-free survival (PFS), overall survival (OS), safety, as well as QoL.

Results

The observed CNS-ORR CNS-ORR of 72.73% (95% CI 51.85–86.85%) in cohort A, 55% (95% CI 34.21–74.18%) in cohort B, and 42.86% (95% CI 21.38–67.41%) in cohort C. The mPFS was 11 months, 8.4 months, and 5.2 months in cohorts A, B, and C, respectively. Diarrhea, accounting for 23.21% of all the patients, was the most common grade 3/4 adverse event related with treatments (6/22 [27.3%] in cohort A, 4/20 [20.0%] in cohort B, and 3/14 [21.4%] in cohort C). However, there were no deaths related with treatments observed. Importantly, the QoL was efficiently maintained throughout the treatment duration.

Conclusion

Pyrotinib and capecitabine combination therapy proved significant effectiveness as well as tolerability in treating HER2-positive BC with BMs, yielding satisfactory results, especially in radiotherapy-naive population.

Keywords:

• breast cancer
• brain metastases
• pyrotinib
• capecitabine
• HER2
• radiotherapy

Data Sharing Statement

All data included in this study are available upon request by contact with the corresponding author.

Ethics Approval

This study was reviewed and approved by the Ethics Committee of The Affiliated Yantai Yuhuangding Hospital of Qingdao University (No. 2023-375).

Acknowledgments

The authors would like to thank patients, nurses and clinicians for their participation in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This study was supported by grants from National Natural Science Foundation of China (Grant No.82103585), Wu JiePing Medical Foundation (Grant No. 320.6750), and Yantai Science and Technology Innovation Development Plan (Grant No. 2022YD042).