Adjuvant Abemaciclib for Locoregional Recurrence of HR-positive, HER2-negative Breast Cancer (JCOG2313, AURA)

NCT07190443 | Recruiting Phase 3

• 2 other identifiers: JCOG2313jRCTs031240666
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Locoregional Recurrence; Abemaciclib; Endocrine Therapy

Outcome Measures

Primary Outcomes (1)

• Invasive disease-free survival

  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.

  Up to 9 years (4 years of accrual and 5 years of follow-up)

Secondary Outcomes (3)

• Distant recurrence-free survival

  Up to 9 years (4 years of accrual and 5 years of follow-up)

• Breast cancer-specific survival

  Up to 9 years (4 years of accrual and 5 years of follow-up)

• Overall survival

  Up to 9 years (4 years of accrual and 5 years of follow-up)

Study Arms (2)

Standard endocrine therapy (Arm A)

ACTIVE COMPARATOR

Participants in Arm A will receive standard endocrine therapy alone as adjuvant treatment following curative-intent local therapy for first locoregional recurrence (LRR) of hormone receptor (HR)-positive, HER2-negative breast cancer. No CDK4/6 inhibitor is administered in this arm.

Drug: Endocrine Therapy (ET): letrozole, anastrozole, exemestane, tamoxifen

Endocrine therapy in combination with abemaciclib (Arm B)

EXPERIMENTAL

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.

Drug: Endocrine therapy + Abemaciclib

Interventions

Endocrine therapy + Abemaciclib DRUG

This intervention consists of adjuvant endocrine therapy in combination with abemaciclib, a CDK4/6 inhibitor, administered to patients with HR-positive, HER2-negative breast cancer who have undergone curative-intent local treatment for their first LRR, including ipsilateral breast tumor recurrence, chest wall recurrence, or regional lymph node recurrence. Abemaciclib is given orally at a dose of 150 mg twice daily for a maximum of 2 years, in accordance with the approved dosing regimen in the adjuvant setting. The choice of endocrine therapy-aromatase inhibitor, tamoxifen, or tamoxifen plus ovarian function suppression-is determined based on menopausal status and prior treatment history.

Endocrine therapy in combination with abemaciclib (Arm B)

Endocrine Therapy (ET): letrozole, anastrozole, exemestane, tamoxifen DRUG

This intervention consists of adjuvant endocrine therapy alone in patients with HR-positive, HER2-negative breast cancer who have undergone curative treatment for their first LRR, including ipsilateral breast tumor recurrence, chest wall recurrence, or regional lymph node recurrence. The choice of endocrine therapy (aromatase inhibitor, tamoxifen, or tamoxifen plus ovarian function suppression) is determined based on the patient's menopausal status and prior treatment history, as specified in the protocol. Treatment is continued for five years or until disease recurrence, unacceptable toxicity, or withdrawal of consent. This intervention does not include CDK4/6 inhibitors.

Standard endocrine therapy (Arm A)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has been diagnosed with the first locoregional recurrence (LRR) after receiving definitive treatment for primary breast cancer. LRR includes one or more of the following:
• (i) Ipsilateral breast tumor recurrence (ii) Ipsilateral chest wall recurrence (iii) Regional lymph node recurrence
• At least one LRR lesion must be confirmed by a biopsy, surgical specimen, or cell block from cytology, and must meet all of the following:
• (i) Pathologically confirmed as invasive breast cancer, or diagnosed as breast cancer in a cytology cell block (in cases where only a cell block is available, the initial primary breast cancer must have been invasive).
• (ii) Hormone receptor (HR) expression is positive. (iii) HER2 expression is negative.
• ※ If multiple lesions are pathologically evaluated and any lesion is HR-negative or HER2-positive, the patient is ineligible.
• No prior diagnosis of distant metastasis of breast cancer.
• Imaging assessment before registration confirms:
• No lymph nodes ≥10 mm in short axis No evidence of distant metastasis
• Age ≥18 years at the time of registration.
• ECOG Performance Status of 0 or 1.
• Chemotherapy for LRR is allowed prior to enrollment.
• The patient does not have bilateral breast cancer.
• No prior history of treatment with CDK4/6 inhibitors.
• Written informed consent has been obtained for participation in this clinical trial.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Japanese Foundation for Cancer Research: lead
• Japan Clinical Oncology Group: collaborator

Study Sites (1)

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Anastrozole; exemestane; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Yukinori Ozaki, MD. PhD.

CONTACT

+81335200111; yukinori.ozaki@jfcr.or.jp

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Physician

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: September 24, 2025
• Study Start: February 7, 2025
• Primary Completion (Estimated): February 6, 2034
• Study Completion (Estimated): February 6, 2035
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

JP (1)