Abstract PS5-09-02: Phase 2 study of adjuvant liposomal doxorubicin and carboplatin for early-stage triple negative breast cancer

Abstract Background: Patients with stage 1 triple negative breast cancer (TNBC) are at high risk of recurrence, given the aggressive nature of the disease. A SEER database review of patients diagnosed with Stage IA TNBC between 2010 and 2019 showed that chemotherapy use increased significantly from 2010-2019 among patients with T1b (p = 0.001) and T1c tumors (p < 0.0001), reaching ≥60% in patients with T1b and ≥70% in patients with T1c tumors across most years. In patients with T1c tumors, chemotherapy was associated with improved BCSS, with a 5-year BCSS of 94.5% for patients receiving chemotherapy vs. 91.2% in the no/unknown chemotherapy group (Adjusted HR = 0.64; 95% CI: 0.48-0.85). Other studies have shown the benefit of adjuvant chemotherapy for stage 1 triple negative breast cancers especially T1c tumors. Given the recurrence free survival and overall survival benefit seen with systemic therapy, guidelines recommend adjuvant chemotherapy for TNBC that are at least 0.6 cm in size. Standard anthracycline-based and taxanes based chemotherapy regimens that have shown benefit in stage II-III breast cancers are routinely used for stage 1 TNBC. However, these regimens are associated with significant risk of neuropathy, alopecia and neutropenia. An investigator-initiated trial at our institution studied the combination of liposomal doxorubicin and carboplatin in the neoadjuvant setting for patients with stage II-III TNBC (ClinicalTrials.gov Identifier: NCT02315196). This study showed that the combination achieved pathologic complete response (pCR) similar to standard regimens with good tolerability. The regimen was well tolerated with minimal risk of alopecia, reduced risk of neuropathy, and lower rates of neutropenia. Selection of liposomal doxorubicin has gained favor due to the lower degree of toxicity, including cardiotoxicity, as compared to conventional doxorubicin while retaining similar efficacy. Based on the results of this study, we are conducting a phase 2 study that will evaluate this regimen in the adjuvant setting for patients with Stage 1 and 2 TNBC. (ClinicalTrials.gov Identifier: NCT05949021) METHODS: The primary objective of this study is to evaluate the efficacy of liposomal doxorubicin and carboplatin in the adjuvant phase for patients with Stage 1 or 2 triple negative breast cancer, as measured by the 5-year disease-free survival (DFS) rate. The current 5-year recurrence-free survival (RFS) is 92.5% compared with 66.5% for patients treated without chemotherapy With 2 years of accrual and 5 years of additional follow-up, we will need 30 patients to achieve 80% power to detect an increase in the five-year survival rate from 66.5% to 84.5% using a 5% level test of survival. Patients diagnosed with early-stage (upto 2.5cm) breast cancer (Estrogen Receptor ≤ 20%; Progesterone receptor ≤ 20% and HER2 negative) who completed primary breast surgery with axillary staging are eligible for the study. Patients must have baseline Left ventricular ejection fraction >50%. Patients will receive liposomal doxorubicin (30mg/m2) and carboplatin (AUC 5) every 4 weeks for 4 cycles. Patients will undergo tumor-informed circulating tumor DNA (ctDNA) monitoring with the Haystack MRD test at baseline, cycles 2 and 4, and every 6 months thereafter for 24 months. After completion of chemotherapy, patient will receive adjuvant breast radiation. Patient will be on follow up for up to 5 years. The study is currently enrolling patients at Rutgers Cancer Institute and Robert Wood Johnson Barnabas Health (RWJBH) affiliate sites in New Jersey. Citation Format: M. George, C. Omene, A. Litvak, G. Raptis, A. Cruz, K. Toomey, S. Kumar, N. Ohri, L. Potdevin, K. Harper, E. L. Gramiccioni, B. Haffty, H. S. Sloane, D. Toppmeyer. Phase 2 study of adjuvant liposomal doxorubicin and carboplatin for early-stage triple negative breast cancer [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 PS5-09-02.