Abstract OT1-04-02: The NAUTILUS trial (No Axillary sUrgical Treatment In clinically Lymph node negative patients after UltraSonography): A prospective multicenter randomized phase III trial (NCT04303715)
Authors: Lee Han-Byoel , Jung Ji Gwang , Chang Jung Min , Chang Ji Hyun , Moon Woo Kyung , Shin Kyung Hwan , Chung Il Yong , Nam Seok Jin , Kim Eun-Kyu , Lee Seeyoun , Park Seho , Lim Woo Sung , Jung Yongsik , Han Wonshik 
Published: March 2022

Abstract
Background. Sentinel lymph node biopsy (SLNB) is currently the standard axillary staging procedure for clinically node-negative breast cancer. According to the ACOSOG Z0011 trial, axillary lymph node dissection (ALND) is now often omitted for clinically node-negative cT1-2 breast cancer patients undergoing breast-conserving surgery even if 1 or 2 metastatic lymph nodes (LN) are identified. It was shown that radiotherapy contributes to regional control of the axilla non-inferior to ALND even in the presence of metastatic LNs. Furthermore, LN metastasis has a limited role in planning adjuvant systemic therapy for hormone receptor-negative breast cancers, and also for hormone receptor-positive, HER2-negative breast cancer with increased use of genomic assays. SLNB is not without complications and omitting axillary staging operation could improve quality of life. Trial Design. In this multicenter, phase III randomized controlled trial including 9 study sites in South Korea, we plan to 1:1 randomize 1734 patients to either omit SLNB (Arm 1) or receive SLNB (Arm 2). Additional ALND can be performed according to the discretion of the surgeon according to the SLNB results. All patients must receive whole-breast irradiation ± tumor bed boost. The recommended upper margin of the radiation field is within 2cm of the humeral head. ClinicalTrials.gov identifier: NCT04303715. Eligibility. Inclusion criteria: women ≥19 years; cT1-2N0M0 unilateral invasive breast carcinoma; all molecular subtypes; clinically and radiologically tumor size ≤ 5cm; clinically- and ultrasonogram-negative axillary lymph nodes, or no tumor on core needle biopsy or fine needle aspiration cytology in case of suspicious lymph nodes; candidate for breast-conserving surgery with no restriction to radiotherapy and adequate systemic therapy. Exclusion criteria: history of any malignancy within 5 years (exception: thyroid cancer and well-treated skin cancer except melanoma); bilateral breast cancer; neoadjuvant chemotherapy; candidate for total mastectomy; male breast cancer. Specific Aims. Primary objective is to test the hypothesis that omitting SLNB for breast cancer is non-inferior to axillary staging operation in terms of 5-year disease-free survival. Secondary objectives are to compare overall survival, distant metastasis-free survival, locoregional recurrence, quality of life assessment, and DFS and axillary recurrence according to molecular subtypes. Statistical Methods. With an expected 5-year DFS of 86% for Arm 2, Arm 1(SLNB omission) will be assessed with a non-inferiority limit of 5% and hazard ratio of 1.4, power 80%, and significance level of 5%, where 224 events are required. The calculated sample size is 780 per study arm, resulting in a total of 1,734 patients assuming a 10% drop-out rate. Present Accrual and Target Accrual. The first patient was randomized on September 15, 2020. As of July 9, 2021, 480 patients have been randomized. Target accrual of 1734 patients is expected to be complete by April 2023, with the primary endpoint analysis expected in 2028.
Citation Format: Han-Byoel Lee, Ji Gwang Jung, Jung Min Chang, Ji Hyun Chang, Woo Kyung Moon, Kyung Hwan Shin, Il Yong Chung, Seok Jin Nam, Eun-Kyu Kim, Seeyoun Lee, Seho Park, Woo Sung Lim, Yongsik Jung, Wonshik Han. The NAUTILUS trial (No Axillary sUrgical Treatment In clinically Lymph node negative patients after UltraSonography): A prospective multicenter randomized phase III trial (NCT04303715) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-02.