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

Condition(s) studied

Investigational drug(s) / intervention(s)

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 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 (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.

Study 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

Primary outcome measure(s)

• 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.

Trial sites (1)

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