Abstract PS4-08-26: Weekly carboplatin and paclitaxel with trastuzumab and pertuzumab (HER2+) or bevacizumab (HER2-) in the neoadjuvant treatment of breast cancer: a phase II trial

Abstract Background: Neoadjuvant chemotherapy (NAC) enables breast conservation and early assessment of treatment response in breast cancer. Anthracycline-based regimens have shown efficacy, but their use is limited by associated long-term toxicities, including cardiotoxicity and secondary leukemia. Weekly taxane-based regimens offer improved tolerability, and dual HER2-targeted therapy with trastuzumab and pertuzumab has demonstrated high pathologic complete response (pCR) rates. For HER2-negative disease, antiangiogenic therapy with bevacizumab may help improve response rates in certain subsets of breast cancer. Objective: To evaluate the efficacy, safety, and tolerability of an anthracycline-free neoadjuvant regimen of weekly carboplatin and paclitaxel with trastuzumab/pertuzumab (HER2+) or bevacizumab (HER2-). Methods: In this single-institution, open-label, phase II trial, patients with histologically confirmed breast cancer (≥1 cm or node-positive) were enrolled. HER2+ patients (Cohort A) received weekly trastuzumab (2 mg/kg; loading 4 mg/kg) and pertuzumab every 3 weeks (420 mg; loading 840 mg). HER2- patients (Cohort B) received bevacizumab 10 mg/kg every 2 weeks. All received paclitaxel (80 mg/m2) and carboplatin (AUC 2) weekly for 12 weeks. Primary endpoint was 2-year progression-free survival (PFS), and secondary endpoints included pCR (RECIST) and toxicity (CTCAE v4.0). Results: 117 patients were randomized (47 to Cohort A, 70 to Cohort B). Baseline characteristics included a median age of 51 years and 80% hormone receptor positivity (HR+). The majority were White (47%) or Asian (24%). Estimated 10-year PFS was 90.3% (95% CI: 81.1-99.5) in Cohort A—89.3% in HR+ (n = 32) and 93.3% in HR- patients (n = 15). In Cohort B, PFS was 68.2% (95% CI: 51.7-84.7), including 59.2% in HR+ (n = 58) and 100% in triple-negative (TNBC) patients (n = 12) (p = 0.0176). Pathologic complete response rates were higher in Cohort A (58.3%) vs. Cohort B (42.6%), especially in HR-/TNBC subsets (88.2% vs. 66.7%). Grade ≥3 treatment-related adverse events (AE) occurred in 28% (Cohort A) and 40% (Cohort B) of patients. Neutropenia was the most common AE in both groups. Neuropathy was reported in 30% (Cohort A) and 51% (Cohort B) of patients, mostly grade 1-2. No cardiotoxicity occurred in Cohort A. Proteinuria was observed in 8.5% of Cohort B patients without treatment delays. Conclusions: This anthracycline-free neoadjuvant chemotherapy (NAC) regimen demonstrated robust efficacy and favorable tolerability in patients with HER2-positive breast cancer, achieving high long-term progression-free survival (PFS) and response rates, particularly among hormone receptor-negative (HR-) subgroups. In HER2-negative disease, clinical outcomes were more heterogeneous, with particularly promising results observed in patients with TNBC. The 10-year follow-up provided critical insights, highlighting favorable outcomes across most subtypes, with the notable exception of HR+/HER2-negative patients. Integration of CDK4/6 inhibitors can help improve outcomes in this subset of patients. In TNBC patients with residual disease, the addition of bevacizumab and immunotherapy may offer therapeutic value. These findings underscore the potential for biomarker-guided treatment strategies and warrant further investigation in prospective clinical trials. Citation Format: F. Shah, S. Gibson, F. Luo, M. Thomas, N. N. Nafissi, E. Vosoughi, S. Lavasani, K. T. Lane, E. H. Lin, K. J. Kansal, H. M. Yong, R. S. Mehta, R. Parajuli. Weekly carboplatin and paclitaxel with trastuzumab and pertuzumab (HER2+) or bevacizumab (HER2-) in the neoadjuvant treatment of breast cancer: a phase II trial [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 PS4-08-26.