Adjuvant Abemaciclib for Locoregional Recurrence of HR-positive, HER2-negative Breast Cancer (JCOG2313, AURA)
- Conditions
- Breast CancerLocoregional RecurrenceAbemaciclibEndocrine Therapy
- Interventions
- Drug: Endocrine therapy + Abemaciclib
- Registration Number
- NCT07190443
- Lead Sponsor
- Japanese Foundation for Cancer Research
- Brief Summary
The JCOG2313 trial is a multicenter, randomized, phase III study designed to evaluate the efficacy and safety of adjuvant abemaciclib in combination with endocrine therapy versus endocrine therapy alone in patients with hormone receptor (HR)-positive, HER2-negative breast cancer who have undergone curative treatment for their first locoregional recurrence (LRR).
Although HR-positive, HER2-negative breast cancer generally has a favorable prognosis, LRR-such as ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, or regional lymph node recurrence-remains a clinically significant event that increases the risk of distant metastasis. While endocrine therapy is standard in this setting, the benefit of adding chemotherapy or other agents remains unclear, and treatment strategies vary widely.
Abemaciclib, a CDK4/6 inhibitor, has shown survival benefit in the adjuvant setting for high-risk early breast cancer. However, its role in post-LRR adjuvant treatment has not been evaluated in a randomized setting. This study aims to determine whether the addition of abemaciclib to endocrine therapy can improve invasive disease-free survival (IDFS) in patients after LRR.
Eligible patients are randomized 1:1 to receive either endocrine therapy alone or endocrine therapy plus abemaciclib (150 mg twice daily for 2 years). The primary endpoint is IDFS. Secondary endpoints include distant recurrence-free survival, breast cancer-specific survival, overall survival, and safety. A total of 290 patients will be enrolled. Randomization is stratified by site of recurrence, endocrine resistance, perioperative chemotherapy, and institution.
Additionally, a prospective ancillary study will assess circulating tumor DNA (ctDNA) as a biomarker for molecular residual disease (MRD). Plasma samples will be collected at predefined time points to evaluate the prognostic and predictive value of ctDNA for relapse and treatment response.
The JCOG2313 trial addresses an unmet need in the management of HR-positive, HER2-negative LRR and may contribute to the establishment of a new standard systemic therapy and personalized monitoring strategies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 290
Not provided
- Presence of active double cancer (synchronous malignancy requiring treatment).
- Ongoing infectious disease requiring systemic therapy.
- Fever ≥38.0°C at the time of registration.
- Women who are pregnant, possibly pregnant, within 28 days postpartum, or breastfeeding; men whose partners intend to become pregnant.
- Psychiatric illness or symptoms that interfere with daily living and may compromise trial participation.
- Ongoing systemic administration (oral or IV) of steroids equivalent to ≥10 mg/day of prednisolone or other immunosuppressive agents.
- Unstable angina (developed or worsened within the past 3 weeks) or myocardial infarction within the past 6 months.
- Uncontrolled hypertension.
- Uncontrolled diabetes mellitus despite continuous insulin or oral antidiabetic therapy.
- Positive for HBs antigen or HCV antibodies (Patients positive for HCV antibodies are not excluded if HCV-RNA is undetectable.)
- Positive for HIV antibodies (HIV testing is not mandatory.)
- Presence of interstitial pneumonia, pulmonary fibrosis, or severe emphysema as diagnosed by chest CT.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Endocrine therapy in combination with abemaciclib (Arm B) Endocrine therapy + Abemaciclib Participants in Arm B will receive endocrine therapy in combination with abemaciclib following curative-intent local treatment for first LRR of HR-positive, HER2-negative breast cancer.
- Primary Outcome Measures
Name Time Method Invasive disease-free survival Up to 9 years (4 years of accrual and 5 years of follow-up) Defined as the time from randomization to the first occurrence of one of the following events:
* Recurrence of invasive breast cancer in the ipsilateral breast, chest wall, or regional lymph nodes (locoregional recurrence);
* Distant recurrence of breast cancer (metastatic disease);
* Invasive contralateral breast cancer;
* Second primary invasive non-breast cancer (excluding non-melanoma skin cancer and in situ cervical cancer);
* Death from any cause. Patients who have not experienced any of the above events will be censored at the date of last disease assessment.
- Secondary Outcome Measures
Name Time Method Distant recurrence-free survival Up to 9 years (4 years of accrual and 5 years of follow-up) Distant Recurrence-Free Survival (DRFS) is defined as the time from randomization to the first occurrence of distant recurrence of breast cancer or death from any cause, whichever occurs first.
Distant recurrence is defined as radiographically or pathologically confirmed metastatic disease outside of the locoregional area.
Patients without events will be censored at the date of last disease assessment.
DRFS is evaluated as a secondary endpoint to assess the effectiveness of treatment in preventing distant metastatic progression.Breast cancer-specific survival Up to 9 years (4 years of accrual and 5 years of follow-up) Breast Cancer-Specific Survival (BCSS) is defined as the time from randomization to death due to breast cancer.
Deaths from other causes (non-breast cancer-related) will be considered competing events and will be censored at the time of death.
Patients who are alive at the time of analysis or lost to follow-up will be censored at the date of last known contact.
BCSS is included as a secondary endpoint to evaluate the disease-specific mortality benefit of the intervention.Overall survival Up to 9 years (4 years of accrual and 5 years of follow-up) Overall Survival (OS) is defined as the time from randomization to death from any cause.
Patients who are alive at the time of analysis or lost to follow-up will be censored at the date of last known contact.
OS will be assessed as a secondary endpoint to evaluate the overall survival benefit of adjuvant abemaciclib in combination with endocrine therapy in the post-recurrence setting.
Trial Locations
- Locations (1)
Cancer Institute Hospital of JFCR
🇯🇵Koto-ku, Tokyo, Japan
Cancer Institute Hospital of JFCR🇯🇵Koto-ku, Tokyo, JapanYukinori Ozaki, MD. PhD.Contact+81335200111yukinori.ozaki@jfcr.or.jp