Abstract PS3-11-17: Pyrotinib as Continued Consolidation Therapy After Anti-HER2 Adjuvant Treatment for Early or Locally Advanced HER2-Positive Breast Cancer: A Multicenter Exploratory Study

Abstract Background: Patients with early or locally advanced HER2-positive breast cancer who have completed standard anti-HER2 adjuvant therapy but harbor high-risk features (e.g., node-positive disease or residual tumor post-neoadjuvant therapy) remain vulnerable to recurrence despite current standard-of-care regimens. Approximately 30% of early breast cancer patients experience recurrence even after standard therapy, with HER2-positive subtypes demonstrating particularly aggressive behavior due to HER2 gene amplification driving tumor progression. Prior landmark studies (APHINITY/KATHERINE) established that dual HER2 blockade or T-DM1 reduces recurrence risk in high-risk populations, yet central nervous system metastases still occur in 25-33% of recurrences, highlighting unmet needs. Preclinical data support pyrotinib’s mechanism as an irreversible EGFR/HER2 dual TKI that inhibits downstream signaling even in trastuzumab-pretreated models, providing rationale for sequential consolidation. This multicenter study evaluated pyrotinib consolidation in this population post-standard anti-HER2 adjuvant therapy. Methods: This open-label exploratory trial enrolled stage II-III HER2-positive breast cancer patients meeting high-risk criteria: node-positive disease without prior neoadjuvant therapy, failure to achieve pathological complete response (non-pCR) post-neoadjuvant therapy, or pCR with additional risk factors (e.g., extensive tumor burden). Eligible participants had completed ≥6 months of trastuzumab/pertuzumab or T-DM1 adjuvant therapy within the preceding year. They subsequently received oral pyrotinib at 400 mg/day for one year. The primary endpoint was 2-year invasive disease-free survival (iDFS), with secondary endpoints including distant DFS (DDFS), overall survival (OS), and safety assessed per CTCAE v5.0. Results: From May 2023 to June 2025, 104 patients were enrolled. As of June 15, 2025, with a median follow-up of 14.5 months, 4 invasive disease-free survival (iDFS) events were observed: 1 local recurrence, 1 bone metastasis, 1 distant metastasis, and 1 death due to cerebral infarction (unrelated to study treatment). Safety analysis demonstrated the following AE profile: Any-grade AEs: Diarrhea (89.4%), decreased appetite (25%), vomiting (6.7%) Grade ≥3 AEs: 11 patients (10.5%) experienced events, most frequently diarrhea (9.6%). Conclusions: Pyrotinib sequential consolidation therapy demonstrated both efficacy and safety in early/locally advanced HER2-positive breast cancer patients with high-risk features following trastuzumab/pertuzumab or T-DM1 adjuvant therapy. The regimen exhibited favorable overall safety with no new safety signals identified. Notably, the incidence of grade ≥3 diarrhea—the most common clinically significant toxicity—was maintained at 9.6% through proactive management strategies. These findings support pyrotinib consolidation as a viable sequential approach for optimizing outcomes in this high-risk population. Citation Format: T. Xia, J. Zhang, L. Xu, C. Yao, H. Yu, D. Wei, X. Lu, L. Wang, Z. Guo, Q. Fang, D. Fu, Q. Hu, K. Tan, K. Luo, H. Pan, X. Liu. Pyrotinib as Continued Consolidation Therapy After Anti-HER2 Adjuvant Treatment for Early or Locally Advanced HER2-Positive Breast Cancer: A Multicenter Exploratory 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 PS3-11-17.