Abstract PO2-01-03: Efficacy of dose-dense and anthracycline-free regimens in neoadjuvant chemotherapy of HER2-positive breast cancer: a single-center matched-cohort study. Preliminary results

Abstract

Abstract Introduction: The efficacy of dose-dense (dd) adjuvant chemo has been proved in numerous clinical trials and meta-analysis. However, it remains unclear whether the intensification of AC (doxorubicine/cyclophosphamide) regimen affects the rate of pathological complete response (pCR) in HER2+ subtype, since the efficiency of thе ddAC-THP (docetaxel/trastuzumab/pertuzumab) regimen with dual anti-HER2-blocade in the neoadjuvant (NA) setting has not been assessed. Anthracycline (A)–containing and A-free regimens (TCHP -docetaxel/carboplatin/trastuzumab/pertuzumab) are considered equivalent, although there are no direct comparative studies to date. Methods: The aim of the study was to assess the rate of pCR of ddAC (once every 2 weeks)-THP NA regimen in comparison with ACq3w (once every 3 weeks)-THP and A-free TCHP regimen in HER2+ stage II-III breast cancer (BC). The study included patients with early HER2+ BC who received NA chemo in a single center from Jan 2017 to Nov 2022. Statistical hypothesis. The study has a 2-step design. It is assumed that the rate of pCR with ddAC will be ≥65%, and with ACq3w≤50%. With a unilateral type I error (α) = 0.05 and a type II error (β) = 0.2, 170 patients should be included in each group. In the absence of significant differences between ddAC and 4ACq3w, groups may be merged into one cohort and compared with TCHP group. It is assumed that A-containing regimens (H1 - pCR 55%) are not inferior to A-free regimen (H0 - pCR 55%). A non-inferiority design is planned, with delta 15%, type I error (α) = 0.05 and type II error (β) = 0.2, 173 people in each group should be included. Here we present preliminary results. Results: A total of 400 patients were included, of which 138 received 4xddAC- 4xTHP, 102 – 4xACq3w-4 x THP, 160 – 6xTCHP. The pCR rate in the whole ddAC-THP group was 55,8%. The majority of patients (77,5%) had stage III disease. After propensity matching analysis to adjust for selection bias 102 patients in each A-containing group were included in the final analysis. The pCR rate was 50% in the ddAC group vs 48% in the ACq3w group (p=0.67). Subgroup analysis, including T, N stage, age, ER status, G, ki67 revealed no advantage of ddAC regimen. Next, both A-groups were merged and after propensity matching analysis 143 patients were included both in A- and TCHP-group. The pCR rate was 53,8% in the A-group vs 60,1% in the TCHP group (p=0.34). Subset analysis demonstrated no benefit of A-regimen across subgroups. Conclusion: Our preliminary results suggest that A-containing and TCHP regimens appear to be equivalent in terms of pCR. In case of choosing AC-THP for NA chemo there’s no need to perform the AC arm in dd way since it does not improve efficacy. Citation Format: Elena Kovalenko, Yaroslav Zhulikov, Maxim Khoroshilov, Igor Vorotnikov, Alexander Petrovskiy, Elena Artamonova. Efficacy of dose-dense and anthracycline-free regimens in neoadjuvant chemotherapy of HER2-positive breast cancer: a single-center matched-cohort study. Preliminary results [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-03.