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

Official title

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.

Overview

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.

Interventions

• Drug Endocrine 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 a
• Drug Endocrine 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 t

Primary outcome measures

• Invasive disease-free survival [Time frame: Up to 9 years (4 years of accrual and 5 years of follow-up)]

Secondary outcome measures (3)

• Distant recurrence-free survival [Time frame: Up to 9 years (4 years of accrual and 5 years of follow-up)]
• Breast cancer-specific survival [Time frame: Up to 9 years (4 years of accrual and 5 years of follow-up)]
• Overall survival [Time frame: Up to 9 years (4 years of accrual and 5 years of follow-up)]

Eligibility criteria

Inclusion criteria

• 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 criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 1 center

• Cancer Institute Hospital of JFCR — Koto-ku

Identifiers

NCT: NCT07190443 · JCOG2313 · jRCTs031240666

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗