Abstract PO1-01-02: Final analysis of neoadjuvant chemotherapy with pegylated liposomal doxorubicin/cyclophosphamide followed by taxanes with full-course trastuzumab/pertuzumab for HER2-positive breast cancer: a single-arm, phase II study

Abstract Background: The optimal neoadjuvant treatment regimen for HER2-positive breast cancer remains unclear, especially regarding the use of anthracycline. We conducted a prospective phase II study to evaluate sequential neoadjuvant chemotherapy with pegylated liposomal doxorubicin (PLD)/cyclophosphamide followed by taxanes in the presence of full-course trastuzumab/pertuzumab in HER2-positive early breast cancer patients. Methods: In this single-arm, open-label, multicenter, phase II study, eligible patients with confirmed HER2-positive early breast cancer were recruited from four independent hospitals. Patients received four cycles of PLD (35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (ypT0/is ypN0, tpCR). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, the proportion of patients requiring breast-conserving surgery, and safety. For biomarkers analysis, tumor tissues were collected at baseline and evaluated for Topoisomerase 2 Alpha (TOP2A) expression assessed prospectively with immunohistochemistry (IHC) assay by independent pathologists. Results: Between May 27, 2020 and May 11, 2022, 78 eligible patients were treated and underwent surgery, of whom 42 (53.8%) patients underwent breast-conserving surgery. After neoadjuvant therapy, 47 (60.3%, 95% CI, 48.5%-71.2%) patients achieved a tpCR in the breast and axilla. The bpCR was observed in 49 (62.8%) patients. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. All (100%) patients achieved disease control since the end of the first cycle. No correlations between clinicopathological variables and pathological response were observed. Grade 3 or worse AEs occurred in 35 (44.9%) patients. Nine (11.5%) patients experienced asymptomatic LVEF reduction (≥10% from baseline), but all with a minimum value of 55%. No treatment-related surgical delay or death occurred. For biomarkers analysis, the status of TOP2A was not found to be associated with pCR or 4th-cycle ORR. Conclusions: This dual HER2-blockade plus polychemotherapy as sequential neoadjuvant regimen demonstrates promising anti-tumor activity and acceptable tolerability for patients with HER2-positive breast cancer. Citation Format: Yaping Yang, Liang Jin, Yudong li, Fengxia Gan, Nanyan Rao, Jun Zhang, Ruifa Feng, Zhenzhen Liu, Qiang Liu. Final analysis of neoadjuvant chemotherapy with pegylated liposomal doxorubicin/cyclophosphamide followed by taxanes with full-course trastuzumab/pertuzumab for HER2-positive breast cancer: a single-arm, phase II study abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-02.