Abstract OT-04-03: Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial

Background Main weaknesses of neoadjuvant chemotherapy (NACT) to avoid axillary dissection (ALND) in patients with clinically node-positive breast cancer are frequent failure of achieving nodal pathologic complete response (pCR) and administration of chemotherapy even though not indicated otherwise in many cases. Tailored axillary surgery (TAS) was designed to selectively remove positive nodes and omit ALND in patients with clinically node-positive breast cancer either in the upfront surgery setting or in case of residual nodal disease after neoadjuvant therapy, which distinguishes this trial from all others ongoing and published. Trial design In this international, multi-center, phase-III, non-inferiority randomized controlled trial, including 61 study sites from six countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS only followed by regional nodal irradiation including the full axilla. TAS consists of selective removal of the sentinel lymph nodes (SLNs) and all palpably suspicious findings, thereby tailoring the extent of axillary surgery to the extent of axillary disease, followed by specimen radiography to document removal of the clip placed in the sampled node. Imaging-guided localization is encouraged to increase the chances of clip removal. All patients undergo adjuvant whole-breast irradiation after breast conserving surgery and chest wall irradiation after mastectomy. Inclusion of internal mammary nodes is recommended irrespective of treatment arm. ClinicalTrials.gov Identifier: NCT03513614. Inclusion criteria - Clinically node-positive breast cancer (all molecular subtypes allowed) - Node-positivity palpable or detectable only by imaging at time of initial diagnosis - Newly diagnosed or isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT. - In case of prior neoadjuvant treatment: residual disease (including residual ITCs) confirmed by pathology at the time of surgery - Clipping of sampled axillary lymph node Exclusion criteria - Absence of clip in the specimen radiography - Palpable disease left behind in the axilla after TAS - No SLN identified in the axilla Specific aims To test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival (DFS) of clinically node-positive breast cancer patients. Secondary objective is to test if quality of life is significantly better with TAS and axillary radiotherapy compared to ALND. Statistical methods With type I error 5% and power 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio (HR) of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm), including one interim analysis for efficacy/futility after 20% of the required events have occurred. The sample size needed is 1500 patients (750 per arm). The HR and one-sided 95% confidence interval will be calculated using a Cox regression model based on the per-protocol set. Present accrual and target accrual The trial was activated on 31 July 2018 and the first patient was randomized on 07 August 2018. As of 03 July 2020, 291 patients have been randomized. Accrual is currently running according to protocol and is planned until end of 2023 with the primary endpoint analysis expected in 2029. Contact information Prof. Dr. Walter Paul Weber, University Hospital Basel; Tel: +41 61 328 61 49; Walter.Weber@usb.ch Citation Format: Walter Paul Weber, Guido Henke, Stefanie Hayoz, Karin Ribi, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Daniel Rudolf Zwahlen, Simone Muenst, Markus Ackerknecht, Florian Fitzal, Mihaly Ujhelyi, Christian Kurzeder, Loic Lelievre, Christoph Tausch, Daniel Egle, Jorg Heil, Zoltan Matrai, Michael Knauer. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-04-03.