Abstract OT2-22-02: Sequencing of anthracyclines and taxanes during neoadjuvant therapy of locally advanced HER2-negative breast cancer (NEOSAMBA Study/LACOG 0419)
Authors: Reinert Tomás , Souza Cristiano P. , Liedke Pedro , Werutsky Gustavo , Testa Laura , Antunes Vivian , Barrios Carlos , Vasconcelos Vivian , Resende Heloísa , Queiroz Geraldo Silva , Guilgen Gisah , Nerón Yeni , Bastos Lilian Arruda , Aleixo Sabina , Cubero Daniel , Magalhães Maria Cristina F. , Coradazzi Ana , de Oliveira Daniela Galvão B. , Nunes João S. , Jesus Rafaela G. , Gössling Gustavo , Bines José 
Published: March 2023

Abstract
Background: Breast cancer (BC) is the most frequent cancer in women in Brazil, with more than 60,000 cases estimated annually. Forty percent of patients present with stages III and IV and neoadjuvant chemotherapy (NACT) remains the mainstay of treatment for locally advanced breast cancer (LABC). Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely because of their later introduction into clinical practice. However, the potential impact of alternative sequencing remains to be studied. A single-center phase II randomized clinical trial conducted in the Brazilian National Cancer Institute showed an improvement in overall survival with taxane-first compared with anthracycline-first sequencing in HER2-negative LABC (Bines J et al, The Oncologist 2020). As a taxane-before-anthracycline sequence carries neither an incremental cost nor increased toxicity, the optimal sequencing of these agents could have significant implications for clinical practice. To confirm this finding, we are currently conducting a multicenter randomized phase III trial comparing a taxane followed by an anthracycline-based regimen with the reverse sequence in the neoadjuvant setting. Trial Design: This randomized, open-label, phase III trial will be conducted in 15 research centers in Brazil. It was approved by the local ethics committee in 2020 and is registered in Clinicatrials.gov with the identifier NCT04540692. Women with HER2-negative LABC are randomized in a 1:1 ratio to anthracycline-before-taxane (AC-T arm) or taxane-before-anthracycline (T-AC arm), stratified by hormone receptor status (positive vs. negative) and axillary lymph node status (N0 vs. N+). The anthracycline-based therapy recommended in this trial is AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every three weeks for four cycles, whilst the taxane-based therapy is either weekly paclitaxel 80 mg/m2 weekly for 12 weeks, paclitaxel 175 mg/m2 every three weeks, or docetaxel 75-100 mg/m2 every three weeks. The use of carboplatin concomitantly with taxane for triple-negative tumors and dose-dense regimens is allowed following institutional guidelines. Further therapies (surgery, radiotherapy, and endocrine therapy) are performed according to the physicians’ discretion. Tumor samples are collected and stored for translational studies. Eligibility: Inclusion criteria: women ≥18 years of age; histologically confirmed HER2-negative breast cancer (by ASCO/CAP guidelines); stage ≥ IIB (if TNBC) or ≥ III (if HR-positive); PS ECOG 0-2 and adequate organ function. Exclusion criteria: previous use of anti-cancer therapies; bilateral BC and pregnancy. Specific Aims: The primary objective is invasive disease-free survival (iDFS). Secondary objectives include pathological complete response (pCR) rates, overall survival (OS) and safety. Statistical Methods: Considering an unicaudal type I error of 0.05, a type II error of 0.2, and an estimated iDFS of 50% in 5 years in the control arm, a total of 227 evaluable patients should be included per arm to demonstrate a HR of 0.7 favoring the taxane-first arm. Estimating a dropout rate of 10%, 494 patients will need to be included in the study. Present Accrual and Target Accrual: A total of 9 sites of 15 planned are activated. The first patient was enrolled on January 12, 2021, and as of June 24, 2022, a total of 113 patients have been accrued. The target goal of 494 patients is expected to be achieved by 2025 and initial study results will be reported by 2026. Funding: Brazilian Health MInistry, Programa Nacional de Apoio à Atenção Oncológica (PRONON), NUP 25000.183207/2019-50. Acknowledgements: CURA Project, SAS.
Citation Format: Tomás Reinert, Cristiano P. Souza, Pedro Liedke, Gustavo Werutsky, Laura Testa, Vivian Antunes, Carlos Barrios, Vivian Vasconcelos, Heloísa Resende, Geraldo Silva Queiroz, Gisah Guilgen, Yeni Nerón, Lilian Arruda Bastos, Sabina Aleixo, Daniel Cubero, Maria Cristina F. Magalhães, Ana Coradazzi, Daniela Galvão B. de Oliveira, João S. Nunes, Rafaela G. Jesus, Gustavo Gössling, José Bines. Sequencing of anthracyclines and taxanes during neoadjuvant therapy of locally advanced HER2-negative breast cancer (NEOSAMBA Study/LACOG 0419) [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 OT2-22-02.