Methods
HER2-positive
ONCOLOGY, DISEASE, METASTATIC BREAST CANCER, METASTATIC DISEASE
PUFFIN was a phase III, randomized, double-blind, placebo-controlled study conducted across 15 centers in China. The protocol was approved by the institutional review board at each participating site. Informed consent was provided from all participants. The study design, eligibility criteria, procedures, assessments, and statistical methods have been reported previously in the primary analysis [Eligible patients were aged ≥ 18 years with HER2-positive (centrally confirmed immunohistochemistry 3 + or in situ hybridization-positive), locally recurrent or metastatic breast cancer. Patients were eligible if they had not received prior treatment for metastatic disease (except for one hormonal regimen before randomization), no prior treatment with HER2-targeting therapies (except trastuzumab in the neoadjuvant or adjuvant settings) or tyrosine kinase inhibitors, and were disease-free for ≥ 12 months. Hormone receptor status was centrally confirmed. Further inclusion criteria included a left ventricular ejection fraction (LVEF) of ≥ 55% at baseline and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Patients were eligible if they had measurable or non-measurable disease.Patients were excluded if they had prior exposure to doxorubicin of ≥ 360 mg/m