Abstract PS3-11-05: Trastuzumab Combined with Pyrotinib and Capecitabine as Postoperative Adjuvant Therapy in Non-Pathological Complete Response HER2-Positive Early Breast Cancer Following Neoadjuvant Therapy: A Multicenter Phase II Study

Abstract Background: HER2-positive early breast cancer patients achieving a pathological complete response (pCR) during neoadjuvant therapy demonstrate a more favorable prognosis. The KATHERINE study indicated that for HER2-positive early breast cancer patients who did not achieve pCR (the presence of residual tumor lesions) after neoadjuvant therapy, the administration of TDM-1 during postoperative adjuvant therapy significantly reduces the risk of disease recurrence compared to trastuzumab. This study aims to evaluate the efficacy and safety of trastuzumab in combination with pyrotinib and capecitabine in HER2-positive early breast cancer patients who did not achieve pCR following neoadjuvant therapy. Methods: This single-arm, open-label, multicenter study enrolled patients with HER2-positive early breast cancer who did not achieve pCR (defined as residual invasive tumor 1 cm or lymph node metastasis) following neoadjuvant therapy. Eligible patients received trastuzumab (initial loading dose of 8 mg/kg followed by 6 mg/kg every three weeks for one year, encompassing both neoadjuvant and adjuvant settings), pyrotinib (400 mg/day for one year post-surgery), and capecitabine (1000 mg/m2 twice daily for six 3-week cycles, with continuation at the investigator's discretion beyond six cycles). Primary prophylaxis with loperamide was administered to mitigate pyrotinib-induced diarrhea. The primary endpoint was 3-year invasive disease-free survival (iDFS), with secondary endpoints including distant disease-free survival (DDFS), overall survival, and safety. This study is registered with ClinicalTrials.gov (identifier NCT05292742). Results: From July 2021 to November 2023, a total of 102 patients were enrolled, all of whom did not achieve pCR following neoadjuvant therapy. As of June 30, 2025, with a median follow-up of 25 months, 2-year iDFS rate was 91.3% (95%CI, 83.3-95.6), and 2-year DDFS rate was 96.8% (95%CI, 90.5-99.0). Regarding safety, 22 patients (21.6%) experienced grade ≥3 adverse events, with the most common being diarrhea (13.7%), white blood cell count decreased (2.0%), and hand-foot syndrome (1.0%). Adverse events led to the treatment interruption of any agent in 66 patients (64.7%), discontinuation of any agent in 8 patients (7.8%), and dose reduction of any agent in 37 patients (36.3%). Conclusions: For patients with HER2-positive early breast cancer who did not achieve pCR (residual invasive tumor 1 cm or lymph node metastasis) following neoadjuvant therapy, the combination of pyrotinib, trastuzumab and capecitabine as postoperative adjuvant therapy appears to improve prognosis. The overall safety profile of the regimen was acceptable, with no new safety signals identified. Primary prophylaxis with loperamide effectively reduced the incidence of grade ≥3 diarrhea during adjuvant therapy with pyrotinib. Citation Format: C. Wang, F. Fu, J. Zhang, S. Lin, Z. Song, Z. Ouyang, X. Chen, M. Lin, G. Cui, G. Han, W. Guo, X. Chen, L. Jia, C. Song, S. Yang, R. Luo, Y. Yan, Y. Zeng, D. Chen, J. Lin, F. Yang, R. Huang, Y. Wang, Z. Zeng, Z. Zhang. Trastuzumab Combined with Pyrotinib and Capecitabine as Postoperative Adjuvant Therapy in Non-Pathological Complete Response HER2-Positive Early Breast Cancer Following Neoadjuvant Therapy: A Multicenter Phase II 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 PS3-11-05.