Abstract PS5-07-24: A randomized phase III trial for evaluating the efficacy of adjuvant abemaciclib in patients with locoregional recurrence of hormone receptor-positive, HER2-negative breast cancer: JCOG2313 (AURA study)

Abstract Background: Hormone receptor (HR)-positive, HER2-negative breast cancer is the most common subtype, accounting for about 70% of all breast cancer cases. Although curative therapy with surgery, radiation, and systemic treatment achieves long-term remission, locoregional recurrence (LRR) occurs in 3-16% of patients, including ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, or regional lymph node recurrence. Patients with LRR are at increased risk for subsequent distant metastasis and death. However, systemic treatment strategies in this setting remain poorly defined, and no standard adjuvant therapy has been established for patients who develop LRR after initial curative therapy. Abemaciclib, a selective CDK4/6 inhibitor, has improved invasive disease-free survival (IDFS) when added to endocrine therapy in high-risk early-stage HR+/HER2− breast cancer, as shown in the monarchE trial. However, its benefit in patients with isolated LRR remains unclear. Whether escalation with abemaciclib improves outcomes in this population requires investigation. Trial Design JCOG2313 (AURA; Abemaciclib Utility for locoregional Recurrence of breast cAncer) is a randomized, open-label, multicenter phase III trial conducted by the Japan Clinical Oncology Group (JCOG). The trial evaluates the efficacy of adding adjuvant abemaciclib to endocrine therapy compared with endocrine therapy alone in patients with first LRR of HR-positive, HER2-negative breast cancer after curative local therapy. Eligible patients are aged 18 years or older with isolated LRR occurring after initial surgery for primary breast cancer, who have undergone complete resection or definitive radiotherapy for LRR with curative intent. Chemotherapy administered before or after local therapy for LRR is permitted. Patients are randomized 1:1 to: Arm A: endocrine therapy alone (tamoxifen or aromatase inhibitor ± LHRH agonist) Arm B: endocrine therapy plus abemaciclib for 2 years The primary endpoint is IDFS. Secondary endpoints include overall survival, distant relapse-free survival, breast cancer-specific survival, and adverse events. The planned sample size is 290 patients to provide 70% power to detect a hazard ratio of 0.59 at a one-sided alpha level of 5%, assuming an accrual period of 4 years and a follow-up period of 5 years. Current Status The trial opened in February 2025 and is currently enrolling patients at participating 51 sites in Japan. A prospective circulating tumor DNA (ctDNA) ancillary study will assess minimal residual disease dynamics before, during, and after treatment using serial plasma samples. This ancillary study aims to evaluate the utility of ctDNA as a biomarker for recurrence risk stratification and treatment response monitoring. Significance This trial addresses a critical unmet need in the management of HR-positive, HER2-negative breast cancer patients with LRR. By evaluating the clinical benefit of abemaciclib in this setting, JCOG2313 may provide evidence to support treatment escalation and improve long-term outcomes. The findings may contribute to establishing future standards of care for patients with LRR. Trial registration:Japan Registry of Clinical Trials (jRCT): jRCTs031240666 Citation Format: E. Tokuda, Y. Ozaki, F. Hara, C. Funasaka, Y. Naito, A. Shimomura, A. Yoshida, N. Maeda, T. Sangai, T. Ishiba, S. Minami, Y. Sagara, Y. Kajiwara, N. Mitome, K. Sasaki, T. Shibata, T. Fujisawa, H. Iwata, T. Shien. A randomized phase III trial for evaluating the efficacy of adjuvant abemaciclib in patients with locoregional recurrence of hormone receptor-positive, HER2-negative breast cancer: JCOG2313 (AURA study) abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-07-24.