PS5-09-11: Dose-dense Paclitaxel with Empegfilgrastim vs weekly Paclitaxel in luminal B HER2-negative early breast cancer (PULSE trial)

Abstract Background. Luminal B HER2-negative breast cancer (BC) is an aggressive subtype with lower chemosensitivity than HER2-positive or triple-negative disease. Standard neoadjuvant chemotherapy (NCT), consisting of doxorubicin-cyclophosphamide (ACq21 or ddACq14) followed by weekly paclitaxel, yields a pathological complete response (pCR) in approximately 20% of patients, which is significantly lower than in other subtypes. Dose-dense (dd) chemotherapy has been shown to improve outcomes in high-risk BC and even in hormone receptor-positive/HER2-negative patients. Paclitaxel can be delivered weekly, biweekly (dose-dense) or every 3 weeks. Evidence suggests that more frequent (weekly or biweekly) paclitaxel dosing improves long term outcomes compared to 3-week schedule. However, no prospective studies have directly compared weekly and biweekly paclitaxel schedules in luminal B early BC. This exploratory trial aims to detect clinically meaningful differences in efficacy of a biweekly paclitaxel schedule supported by empegfilgrastim in comparison to historical weekly paclitaxel and provide early data to inform the planning of a future phase III trial. Aim. To determine whether a biweekly paclitaxel regimen is not inferior in efficacy (as measured by pCR rate) to the standard weekly paclitaxel regimen in patients with luminal B HER2-negative early or locally advanced BC receiving NCT. Study Design. Prospective, single-center, open-label, non-inferiority phase II trial using historical control. Patients in the intervention group will be treated prospectively and compared to a historical cohort treated with weekly paclitaxel. Matching will be performed in a 1:3 ratio using key clinical and pathological variables (age, clinical stage, Ki-67, tumor grade, ER and PR expression). Population. Eligible patients are adult women (≥18 years) with histologically confirmed luminal B breast cancer, defined as estrogen receptor (ER≥1%) positive, HER2-negative tumors with Ki-67 ≥30%. Patients must have early or locally advanced disease (T2-T4 and/or N1-N3, M0) for which NCT is appropriate. Key exclusions include HER2-positive tumors, metastatic disease and any prior chemotherapy for the current cancer. Treatment. All patients in the prospective arm will receive 4 cycles of ddAC (doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 every 14 days) with empegfilgrastim 7.5 mg as G-CSF support. This is followed by 4 cycles of biweekly paclitaxel (175 mg/m2 every 14 days) with empegfilgrastim 7.5 mg support. The historical control arm will include patients previously treated with AC (q21 or q14) followed by weekly paclitaxel (80 mg/m2 weekly ×12).Primary endpoint is pCR rate, defined as no residual invasive cancer in breast and lymph nodes (ypT0/is, ypN0) at surgery. Secondary endpoints include RCB 0-I rate, event-free survival, relative dose intensity, breast conservation rate, treatment completion rates, and safety outcomes such as neuropathy, neutropenia, and febrile neutropenia. Statistical Analysis. Analyses will be conducted on an intention-to-treat basis. The primary endpoint will be compared between groups using a one-sided 95% confidence interval to evaluate non-inferiority, with a non-inferiority margin of 10%. Propensity score matching (1:3) will balance baseline characteristics. Logistic regression adjusted for matching strata will estimate odds ratios. Secondary endpoints will be analyzed using Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards models for time-to-event outcomes. Sample Size Justification. Assuming a pCR rate of 20% in the historical weekly paclitaxel group and a non-inferiority margin of 10%, a sample size of 102 patients in the prospective biweekly arm and 307 matched historical controls (1:3 ratio) achieves 80% power with one-sided α=0.05. Citation Format: P. Krivorotko, N. Amirov, V. Mortada, A. Emelyanov, R. Pesotskiy, E. Zhiltsova, T. Tabagua. Dose-dense Paclitaxel with Empegfilgrastim vs weekly Paclitaxel in luminal B HER2-negative early breast cancer (PULSE 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 PS5-09-11.