Evaluating the Response-Guided Therapy With Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer (JCOG2402, Young HOPE)

Phase 3RecruitingNCT07671885

Tokyo Women's Medical University950 enrolled

Overview

Young HOPE/JCOG2402 is a multicenter, randomized phase III study designed to evaluate response-guided therapy following neoadjuvant endocrine therapy to optimize adjuvant treatment in premenopausal HR+/HER2- Breast Cancer. Premenopausal women with intermediate-risk HR-positive/HER2-negative breast cancer derive benefit from the addition of chemotherapy to endocrine therapy. However, previous studies have demonstrated that patients who achieve an endocrine response (Ki-67 ≤10%) following neoadjuvant endocrine therapy have excellent outcomes without chemotherapy, irrespective of menopausal status. These findings suggest that endocrine therapy response may serve as a predictive biomarker to identify premenopausal patients who can safely omit chemotherapy. The primary objective of this study is to evaluate the non-inferiority of an ET response-guided treatment strategy compared with standard surgery followed by adjuvant therapy. The study aims to increase the proportion of patients who can be treated with endocrine therapy alone by omitting chemotherapy in those with highly endocrine-sensitive disease. Eligible patients are randomized 1:1 to upfront surgery or neoadjuvant endocrine therapy with an aromatase inhibitor and ovarian function suppression. The primary endpoint is EFS. Secondary endpoints include overall survival, relapse-free survival, distant recurrrence-free survival, HR-QOL, the rate of endocrine therapy alone in adjuvant therapy, ET response rate in an Arm B, the rate of non-menopause and safety. A total of 950 patients will be enrolled. Randomization is stratified by cN0 vs cN1, HG1 or 2 vs 3, and institution. The JCOG2402 trial addresses an unmet need in adjuvant therapy of premenopausal HR-positive, HER2-negative breast cancer with intermediate risk and may contribute to the establishment of a new treatment strategy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

Adjuvant systemic therapy based on pathological findings and ET responseDRUG

If patients with Oncotype DX RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients) have an ET response (Ki-67 ≤10%), they are treated with endocrine therapy plus OFS without chemotherapy. Patients without an ET response or with high risk (RS ≧26) receive chemotherapy and endocrine therapy with OFS. Patients with RS ≤ 15 (pN0) are treated with tamoxifen. Adjuvant chemotherapy for pN0 and pN1 is TC and anthracycline-taxane, respectively. Aromatase inhibitor or tamoxifen is co-administered with a LHRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of LHRH agonist and dosing schedule is per investigator's discretion. Endocrine treatment beyond 5 years is at the investigator's discretion.

Adjuvant systemic therapy based on pathological findingsDRUG

Patients with Oncotype DX recurrence score (RS) ≧16 (pN0) or pN1 are treated with chemotherapy and endocrine therapy with ovarian function suppression (OFS). Adjuvant chemotherapy for pN0 and pN1 is TC and anthracycline-taxane, respectively. Aromatase inhibitor or tamoxifen co-administered with a LHRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of LHRH agonist and dosing schedule is per investigator's discretion. Endocrine treatment beyond 5 years is at the investigator's discretion. Patients with RS ≤ 15 are treated with tamoxifen.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Women aged 18 years or older 2. ECOG PS 0-1 3. HR-positive/HER2-negative breast cancer 4. ER expression ≥ 10% 5. cN0; HG 1: 3 cm\<T≤5 cm, HG 2: 2 cm\<T≤5 cm or HG3: 1 cm\<T≤5 cm cN1; cT\<5 cm and HG 1/HG 2 6. Premenopausal women with spontaneous menses within 12 months 7. No distant metastasis of breast cancer 8. No prior diagnosis of breast cancer. 9. No multiple regions of breast cancer 10. No contralateral breat cancer 11. Adequate organ function Exclusion Criteria: 1. Presence of active double cancer (synchronous malignancy requiring treatment). 2. Ongoing infectious disease requiring systemic therapy. Fever ≥38.0°C at the time of registration. 3. Women who are pregnant, possibly pregnant, within 28 days postpartum, or breastfeeding; men whose partners intend to become pregnant. 4. Psychiatric illness or symptoms that interfere with daily living and may compromise trial participation. 5. Ongoing systemic administration (oral or IV) of steroids equivalent to ≥10 mg/day of prednisolone or other immunosuppressive agents. 6. Unstable angina (developed or worsened within the past 3 weeks) or myocardial infarction within the past 6 months. 7. Uncontrolled hypertension. 8. Uncontrolled diabetes mellitus despite continuous insulin or oral antidiabetic therapy. 9. Positive for HBs antigen or HCV antibodies (Patients positive for HCV antibodies are not excluded if HCV-RNA is undetectable.) 10. Positive for HIV antibodies (HIV testing is not mandatory.) 11. Presence of interstitial pneumonia, pulmonary fibrosis, or severe emphysema as diagnosed by chest CT.

Locations (49)

Akita University Hospita

Akita, Japan

RECRUITING

Chiba Cancer Center

Chiba, Japan

RECRUITING

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan

RECRUITING

Fukushima Medical University Hospital

Fukushima, Japan

Outcomes

Primary Outcomes

Event free survival

Time from randomization to the first diagnosis of local invasive recurrence, regional recurrence, distant recurrence, contralateral invasive breast cancer, inoperable progressive disease during neoadjuvant endocrine therapy, second primary invasive non-breast cancer (excluding non-melanoma skin cancer and in situ cervical cancer), or death from any cause

Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)

Secondary Outcomes

Overall survival

Time from randomization to death from any cause

Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)

Relapse-free survival

Time from randomization to the first diagnosis of relapse or death from any cause

Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)

Distant recurrence-free survival

Time from randomization to the first diagnosis of distant recurrence of breast cancer or death from any cause

Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)

Evaluating the Response-Guided Therapy With Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer (JCOG2402, Young HOPE)

Overview

Conditions

Interventions

Eligibility

Locations (49)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts