Abstract P3-07-23: Defendor Special: Primary empegfilgrastim prophylaxis (prolonged G-CSF) for optimal treatment outcomes in high risk early breast cancer cohort. The interim analysis
Authors: Sorokina Irina , Ganshina Inna , Ibragimova Tansuly , Bondareva Irina , Zhukova Lyudmila 
Published: March 2023

BACKGROUND Relative dose intensity (RDI) of chemotherapy (CT) &lt; 85% significantly decrease therapy efficiency (including overall survival) in early breast cancer (BC) patients (pts). Pathological complete response (pCR) reflects better outcomes and correlates with the RDI of neoadjuvant CT (NAC). Neutropenia is the most common AE leading to RDI drop. Recent studies are demonstrate that G-CSF could switch immunosuppressive tumor microenvironment via neutrophils plasticity. In early BC neutrophils, can mediated antitumor responses by direct killing of tumor cells and by participating in cellular networks that mediate antitumor resistance. Primary G-CSF prophylaxis (PP) with prolonged G-CSF may be an option for optimal therapy results. This multicenter prospective study was designed to evaluate the RDI and treatment outcomes of cytotoxic therapy under PP by empegfilgrastim (E) in pts with high-risk early BC. METHODS High-risk BC pts (n=195) with II-III stages are getting NAC of the following regimens: 4 dose dense doxorubucin/cyclophosphamide with E followed by 12 weekly paclitaxel/carboplatin (4ddAC+E/12P+carbo) for triple negative (TN) pts or 4 dose dense doxorubucin/cyclophosphamide with E followed by 4 dose dense paclitaxel with E (4ddAC+E/4ddP+E) for HR+HER2- pts and 6 docetaxel/carboplatin trastuzumab/pertuzumab (TCHP+E) for HER2+ pts. RDI of therapy course was primary endpoint and presented here for pts who completed the planned regimen. For each agent, the planned and actual dose intensity were calculated by dividing the total cumulative dose by treatment duration in days. RDI was calculated for each single agent in CT regimen and for CT regimen in total. These descriptive analyses were performed for the whole CT regimen. The secondary endpoint: pCR (ypT0/is, ypN0) is also presented here. ClinicalTrials.gov No NCT04905329. RESULTS At the data cut-off (April’2022) 111 pts with BC (HER2+ (n=56); HR+ HER2- (n=17); TN (n=38)) underwent ≥ 1 cycle of NAC with E. The planned CT course completed in 67 (60%) BC pts. RDI≥85% were fixed in 56 (84%) pts: 93% RDI for 4ddAC+E/4ddP+E regimen; 90,3% RDI for 6TCHP+E; 94,1% RDI for 4ddAC+E/12P+carbo. Preliminary, in HER2+ BC pts pCR rate exceeds KRISTINE trial data despite a more enriched pts’ population with poor prognosis (36% pts with IIIB - III C and 65% pts with IIA-IIIA stages per TNM v.8): 93,3% (15 pts HR-) and 70,4% (34 pts HR+). In TNBC pts pCR rate is 56% (9 pts) according to historical control. In HR+ HER2- BC – pCR rate is 20% (10/17 pts under surgery). Neutropenia as a reason of RDI drop was in 1 (0,9%) case in HER2+BC pt. The mature data are awaited. CONCLUSION PP with E allows to maintain RDI efficiently and safely in high-risk recurrence pts populations. High pCR rate under E in HER2+ BC pts focused on further confirmation with translational research. KEY WORDS: empegfilgrastim, neutropenia, pCR, dose intensity, G-CSF, breast carcinoma, neoadjuvant therapy

Citation Format: Irina Sorokina, Inna Ganshina, Tansuly Ibragimova, Irina Bondareva, Lyudmila Zhukova. Defendor Special: Primary empegfilgrastim prophylaxis (prolonged G-CSF) for optimal treatment outcomes in high risk early breast cancer cohort. The interim analysis. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-23.