Completion axillary lymph node dissection for the identification of pN2–3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial

• Published in: The lancet oncology 2024, Vol.25 (9), p.1222-1230
• Main Authors: de Boniface, Jana, Appelgren, Matilda, Szulkin, Robert, Alkner, Sara, Andersson, Yvette, Bergkvist, Leif, Frisell, Jan, Gentilini, Oreste Davide, Kontos, Michalis, Kühn, Thorsten, Lundstedt, Dan, Offersen, Birgitte Vrou, Olofsson Bagge, Roger, Reimer, Toralf, Sund, Malin, Christiansen, Peer, Rydén, Lisa, Filtenborg Tvedskov, Tove
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aminopyridines - therapeutic use; Axilla; Benzimidazoles; Biopsy; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cancer and Oncology; Cancer och onkologi; Chemotherapy, Adjuvant; Clinical Medicine; Clinical outcomes; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 6 - antagonists & inhibitors; Disease-Free Survival; Dissection; ErbB-2 protein; Estrogens; Female; Humans; Invasiveness; Klinisk medicin; Lymph Node Excision; Lymph nodes; Lymphatic Metastasis; Lymphatic system; Lymphedema; Medical and Health Sciences; Medicin och hälsovetenskap; Metastases; Metastasis; Middle Aged; Morbidity; Neoplasm Staging; Patients; Protein Kinase Inhibitors - therapeutic use; Quality of life; Questionnaires; Radiation therapy; Surgery; Survival
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(24)00350-4

In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1–2, grade 1–2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2–3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial. In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1–T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1–2, histological grade 1–2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing. Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND a