Abstract 5975: Long-acting G-CSF empefilgrastim with dose-dense chemotherapy for patients with stage II-III TNBC: Defendor Special trial, primary analysis
Authors: Inna Ganshina, Elena Artamonova, Elena Lubennikova, Olga Gordeeva, Mariam Manukyan, Daria Filonenko, Lyudmila Zhukova, Irina Sorokina
Journal: Cancer Research (2025)

Abstract Background: Dose-dense neoadjuvant chemotherapy (NAC) provides the best efficacy results, irrespective of aPD-1 combinatory agent use for the most aggressive subtype of breast cancer - triple negative (TNBC). Maintaining relative dose intensity (RDI)≥85% of NAC and RCB 0-1 achievement after NAC are significantly associated with improvement of patient’s prolonged long-term efficiency outcomes. Neutropenia is one of the keys limiting adverse event (AE) reducing RDI. Long-acting G-CSF is an essential component for balanced RDI’ maintenance. Here we present the results of efficacy and safety of original prolonged G-CSF empegfilgrastim for patients’ (pts) cohort with TNBC under dose-dense therapy regimen from Defendor Special investigator-initiated trial. Methods: High-risk stage II-III BC pts (n=60) received NAC: 4 dose-dense doxorubicin/cyclophosphamide (ddAC) with empegfilgrastim → 12 QW paclitaxel/carboplatin. RDI was primary endpoint and presented here for pts who completed the planned regimen. Analyses was performed for the 4ddAC part, paclitaxel/carboplatin part, and whole regimen. Secondary endpoints: pCR (ypT0/is, ypN0), RCB rate and safety are also presented here. NCT04905329. Results: 60 pts were included and received at least 1 dose of NAC with empegfilgrastim at the time of data cut-off. Pts with initially negative prognosis are enriched in the population: 38 (63%) pts with IIIB/C stages, 36 (60%) pts with G3. 57 (95%) pts completed the planned course of sequential therapy, 3 (5%) pts had disease progression (local or distant) that precluded definitive surgery (initially resistant population). RDI≥85% of the whole NAC course was achieved in 54 (96%) pts. Median RDI for ddAC part was 100% and 94% - for paclitaxel/carboplatin part. pCR rate of operable stages was 50% and 43% - for locally advanced stages. 64% of pts in the whole population switched to the favorable prognosis group due to achieving the RCB level of 0-1. There were 58% of pts with initially stages IIIB/C and RCB 0-1 level was 60% in this group. Neutropenia as a reason for therapy discontinuation was in 1 pts for the whole NAC regimen. Main reasons for premature interruption were neuropathy or thrombocytopenia associated with paclitaxel/carboplatin use. Conclusions: Empegfilgrastim allows for maintained RDI≥85% of sequential NAC therapy with dose-dense regimen part effectively and safely. Balanced neutrophil count could be able improve efficacy results and switched pts prognosis to favorable for majority of pts. In case of limited access to aPD-1 therapy, prolonged G-CSF (empegfilgrastim) becomes a full-fledged agent in a dose-dense regimen that can determine the outcome for patients with TNBC. Final analysis with long-term outcomes is awaited. Citation Format: Inna Ganshina, Elena Artamonova, Elena Lubennikova, Olga Gordeeva, Mariam Manukyan, Daria Filonenko, Lyudmila Zhukova, Irina Sorokina. Long-acting G-CSF empefilgrastim with dose-dense chemotherapy for patients with stage II-III TNBC: Defendor Special trial, primary analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5975.