Discussion
HER2-positive MBC, neutropenia, leukopenia, diarrhea
NEUTROPENIA, LEUKOPENIA, CNS METASTASES
Our findings demonstrate that the combination of pyrotinib with docetaxel shows promising antitumor activity and provides a PFS benefit in patients with HER2-positive MBC when used as a first-line treatment. Importantly, no new safety concerns were observed during the study. Notably, the oral formulation of pyrotinib offers a significant advantage over trastuzumab, which requires intravenous injection. The convenience of oral administration is particularly beneficial for patients, especially after completing the docetaxel treatment. In our study, several patients have been on maintenance pyrotinib for over 3 years, suggesting that the ease of oral administration may improve patient adherence to the treatment regimen.Dual-targeted therapy has become the standard first-line treatment for patients with MBCThe therapeutic landscape for HER2-positive MBC is undergoing significant transformation, propelled by the advent of advanced agents such as ADCs, exemplified by trastuzumab deruxtecanApproximately 30-40% of patients with HER2-positive MBC develop CNS metastases after trastuzumab treatmentIn our study, more than 30% of patients had received trastuzumab in their (neo)adjuvant setting, which was a higher proportion compared to previous studiesDiarrhea has been a common AE associated with the use of small molecule anti-HER2 TKIs such as lapatinib, pyrotinib, and neratinibPrevious studies have consistently demonstrated that patients harboring This study has several limitations that should be considered when interpreting the results. Firstly, it is a single-arm study with a limited sample size, which may introduce potential bias and limit the generalizability of the findings. Secondly, the study only enrolled Chinese patients, and the efficacy and safety of pyrotinib plus docetaxel in other populations remain unknown. Further research in diverse populations is needed to validate the results. Thirdly, the OS data was still immature at the time of analysis, and longer-term follow-up is ongoing. Fourthly, the statistical significance between biomarkers and treatment outcomes was challenging to detect due to the small number of patients suitable for biomarker analysis. Additionally, some mutations were infrequently detected, and caution should be exercised when interpreting these results.Pyrotinib in combination with docetaxel demonstrated promising antitumor activity and showed a significant PFS benefit for patients with HER2-positive MBC in the first-line setting. The use of loperamide as prophylaxis effectively reduced the incidence of diarrhea, while prophylactic PEG-rhG-CSF administration was successful in preventing leukopenia and/or neutropenia. Future research with larger and more diverse patient populations will be essential to validate and expand on these promising results.