RecruitingPhase 3NCT07190443

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

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 Trial.

Sponsor

Japanese Foundation for Cancer Research

Enrollment

290 participants

Start Date

Feb 7, 2025

Study Type

INTERVENTIONAL

Conditions

Breast Cancer Abemaciclib Locoregional Recurrence Endocrine Therapy

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria15

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.

Exclusion Criteria12

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.

Interventions

DRUGEndocrine therapy + Abemaciclib

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.

DRUGEndocrine Therapy (ET): letrozole, anastrozole, exemestane, tamoxifen

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.