Abstract PS3-10-29: Ner-tree study interim analysis of safety and patient-reported outcomes in patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) treated with neratinib in China

Abstract Background Neratinib, an oral irreversible pan-HER tyrosine kinase inhibitor, was approved in 2020 in China for the extended adjuvant treatment of HER2+ early breast cancer (EBC) adult patients. Diarrhea is the most common treatment-related adverse event associated with neratinib and an important factor impacting patients’ quality of life during therapy. Evaluating the effectiveness of anti-diarrheal prophylaxis measures and patient-reported outcomes in real-world settings is essential. Method NER-Tree is an ongoing, prospective, multi-center, non-interventional study (NCT05491057) that aims to enroll 500 patients with HER2+ early breast cancer (EBC) starting 1-year extended adjuvant neratinib. Diarrheal prophylaxis for neratinib was not required. Prespecified interim analyses are planned after the recruitment of 250 and 500 patients. Primary and secondary objectives are to characterize real-world treatment patterns and assess neratinib's safety profile including diarrhea, respectively. The exploratory objectives include patient-reported quality of life (QoL), and pattern of breast cancer recurrences. Here we report safety data in the second interim analysis, focusing on diarrhea management and patient-reported outcomes. Results As of 28 October 2024, 500 patients were included in the analysis. Diarrhea (86.4%), nausea (18.2%), fatigue (15.6%), and decreased appetite (14.4%) were the most common AEs of any grade. Serious adverse events (SAEs) were reported in 3.4% of the patients. Diarrhea was predominantly reported as Grade 1 or 2 (69.6%), while Grade 3 diarrhea was reported in 16.8% of the patients. No grade 4 diarrhea was observed. The median time from the initiation of neratinib treatment to the onset of diarrhea was 3.0 days (interquartile range [IQR] 2.0,6.0). Diarrhea was the most common adverse event leading to dose reduction (14.4% of cases vs. 18.2% for all adverse events combined), dose interruption (18.0% vs. 33.6%), and permanent discontinuation (4.2% vs. 6.8%). Patients who initiated neratinib at