Abstract PS3-11-07: Real-world use of neratinib in her2-positive early breast cancer in korea: updated follow-up from a multicenter observational study

Abstract Background: Extended adjuvant neratinib improves invasive disease-free survival (iDFS) in patients with HER2-positive, hormone receptor-positive (HR+) early breast cancer (eBC) following adjuvant trastuzumab-based therapy, as shown in the ExteNET trial. However, real-world evidence in the post-pertuzumab/T-DM1 era is limited. We report updated outcomes from a Korean multicenter cohort. Methods: We retrospectively analyzed 48 HR+/HER2+ eBC patients who received neratinib between May 2022 and June 2025 at four academic hospitals in Korea. Patients had completed trastuzumab-based neoadjuvant or adjuvant therapy within 12 months prior to initiating neratinib. Data on prior regimens, neratinib administration, adverse events (AEs), and recurrence were collected. The primary endpoint was treatment pattern and tolerability; the secondary endpoint was iDFS. Results: The median age was 50 years (range, 37-66), and all patients were hormone receptor-positive. Most patients (75%) received the TCHP regimen. Post-neoadjuvant HER2-targeted therapies included: trastuzumab emtansine in 20 patients (41.7%), trastuzumab plus pertuzumab in 16 (33.3%), trastuzumab alone in 11 (22.9%), and trastuzumab deruxtecan in 1 patient (2.1%). Neratinib was initiated at 240 mg/day in 46 patients (95.8%), and at 120 mg/day with subsequent dose escalation in 2 patients. The median treatment duration was 11.2 months (range, 1.0-12.0). Diarrhea prophylaxis was administered in 85.4% of patients. The most common treatment-emergent adverse event (TEAE) was diarrhea (88.6%), followed by fatigue (29.5%) and skin reaction (20.5%), mostly grade 1 or 2. Grade ≥3 toxicities occurred in 12.5% of patients. Adverse events led to dose modifications in 9 patients (18.8%), including both dose interruptions and reductions. Permanent discontinuation due to AEs occurred in 4 patients (8.3%); AEs leading to dose modification included: diarrhea (n=6), nausea (n=2), oral mucositis (n=1), and duodenal ulcer (n=1). AEs leading to discontinuation included: vomiting (n=1), COVID-19 (n=1), diarrhea (n=1), nausea (n=1), fever (n=1), and duodenal ulcer (n=1). At a median follow-up of 11.8 months, no invasive disease recurrence was observed. Among the 48 patients, 31 completed the full 1-year course of neratinib, 7 remained on treatment, and 7 were lost to follow-up. Conclusion: In this real-world Korean cohort, neratinib was commonly used after pertuzumab or T-DM1. Treatment was feasible and generally well tolerated with appropriate supportive care. No recurrence was observed during early follow-up. To our knowledge, this represents the first Asian real-world data on neratinib in the extended adjuvant setting. Funding Source: This work was supported by BIXINK Therapeutics Co., Ltd. Citation Format: S. Kim, S. Kim, K. Shin, J. Lee, J. Kim, Y. Moon. Real-world use of neratinib in her2-positive early breast cancer in korea: updated follow-up from a multicenter observational study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-11-07.