Abstract PS3-11-27: Twelve Weekly Neoadjuvant Paclitaxel and Carboplatin with Trastuzumab and Pertuzumab: A Novel De-escalation Strategy

Abstract Introduction: The standard treatment regimen for early HER2-positive disease consists of 18 weeks of carboplatin, docetaxel, trastuzumab, and pertuzumab. This regimen associated with significant toxicities. Therefore there is a pressing need for tailored de-escalation strategies that maintain efficacy while reducing treatment burden. Methods: We performed a retrospective analysis of a unique cohort of patients with stage II and III HER2 positive breast cancer prescribed a de-escalated neoadjuvant regimen of 12 weekly cycles of paclitaxel and carboplatin along with trastuzumab, and pertuzumab (12wTCHP). Results: Of the 43 patients who received 12wTCHP regimen, 31 (72%) had stage IIA disease, 27 (63%) were positive for estrogen receptor (ER), and 40 (93%) had invasive ductal carcinoma (IDC). The median age was 65 (IQR 51-75). The most prevalent grade 3-4 toxicities were neutropenia (17%) and diarrhea (17%). No treatment-related deaths occurred. The median relative dose intensity (RDI) of paclitaxel and carboplatin was 79%, with a higher RDI in the stage IIA stage compared to stage IIB and III (82% vs. 60%, p=0.003). The pathological complete response (pCR) rate was 63%. In the ER-positive and ER-negative subtypes, the pCR rate was 56% and 75% respectively. During a median follow-up of 20 months, invasive disease recurrence occurred in two patients (5%). Of these, none of the 29 patients with stage IIA IDC experienced a recurrence. Conclusions: A de-escalated neoadjuvant approach (12wTCHP) for early-stage HER2-positive breast cancer demonstrated a favorable safety profile, high pCR rate, and low recurrence rate. Citation Format: Y. Leshem, I. Golomb, Y. Bar, S. Strulov Shachar, A. Zubkov, N. Khadmy, A. Sonnenblick. Twelve Weekly Neoadjuvant Paclitaxel and Carboplatin with Trastuzumab and Pertuzumab: A Novel De-escalation Strategy [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 PS3-11-27.