Chemo-free in Older (≥65) Node-Positive ER+/HER2- Breast Cancer

Phase 3

Not yet recruiting

• Conditions: Breast Cancer; Adjuvant Therapy
• Interventions: Drug: Chemotherapy; Drug: CDK4/6 Inhibitor; Drug: Endocrine therapy

• Registration Number: NCT07005557
• Lead Sponsor: Fudan University

Brief Summary

This study is a prospective, open-label, multicenter, randomized controlled Phase III clinical trial. Based on the use of CDK4/6 inhibitors in endocrine-sensitive luminal-type (ER+/HER2-) breast cancer, it aims to explore the possibility of chemotherapy exemption in elderly patients (aged \>65 years) with lymph node-positive, HR+/HER2- breast cancer.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-05-03
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-03
• Last Update Submitted: 2025-06-03
• Study First Posted: 2025-06-05
• Last Update Posted: 2025-06-05
• Study Start: 2025-06-15
• Primary Completion: 2030-05-15
• Study Completion: 2035-05-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 1244

Inclusion Criteria

-1. Age: Female patients aged ≥65 years. 2. Disease Status: Histologically confirmed early-stage breast cancer after surgery with ER expression ≥50% AND one of the following:

1. ≥4 positive lymph nodes
2. 1-3 positive lymph nodes plus at least one of the following high-risk features: i. High-risk multigene assay result ii. Primary tumor size >2 cm iii. Histologic grade 3 iv. Lymphovascular invasion (LVI) positive v. Ki-67 >20% 3. Treatment Acceptance: Willing to receive adjuvant CDK4/6 inhibitor therapy. 4. Performance Status: ECOG score 0-2. 5. Adequate Organ Function:

a) Hematology (within 14 days, no transfusion): i. Hemoglobin (Hb) ≥90 g/L ii. Absolute neutrophil count (ANC) ≥1.5×10⁹/L iii. Platelets (PLT) ≥100×10⁹/L b) Biochemistry: i. Total bilirubin (TBIL) ≤1.5×ULN ii. ALT/AST ≤3×ULN iii. Serum creatinine (Cr) ≤1×ULN iv. Estimated creatinine clearance (CrCl) >50 mL/min (Cockcroft-Gault formula) 6. Consent & Compliance: Willing to participate, sign informed consent, and comply with follow-up.

Exclusion Criteria

• 1. Patients who have received neoadjuvant therapy (including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy).

  2. Bilateral breast cancer. 3. History of other malignancies, except: Cured basal cell carcinoma of the skin； Carcinoma in situ of the cervix 4. Distant metastasis (any site). 5. Any T4 lesion (UICC 1987 TNM staging), including: Skin invasion; Fixed mass adherence; Inflammatory breast cancer 6. Concurrent participation in other clinical trials. 7. Severe organ dysfunction (cardiac, pulmonary, hepatic, or renal), including:

  a) LVEF <50% (by echocardiography) b) Major cardiovascular/cerebrovascular events within 6 months before randomization: i. Unstable angina ii. Chronic heart failure iii. Uncontrolled hypertension (>150/90 mmHg) iv. Myocardial infarction or stroke c) Poorly controlled diabetes mellitus d) Severe hypertension 8. Known allergy to taxane-based drugs or their excipients. 9. Severe or uncontrolled infections. 10. History of psychoactive drug abuse (unable to abstain) or psychiatric disorders.

  11. Patients deemed ineligible by investigator assessment. 12. Refusal to receive adjuvant CDK4/6 inhibitor therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Chemotherapy	Chemotherapy, endocrine therapy, or CDK4/6 inhibitors, administered at the physician's discretion.
Control	CDK4/6 Inhibitor	Chemotherapy, endocrine therapy, or CDK4/6 inhibitors, administered at the physician's discretion.
Control	Endocrine therapy	Chemotherapy, endocrine therapy, or CDK4/6 inhibitors, administered at the physician's discretion.
Chemo-free	CDK4/6 Inhibitor	A chemotherapy-sparing approach using CDK4/6 inhibitor combined with aromatase inhibitor (minimum 5-year duration).
Chemo-free	Endocrine therapy	A chemotherapy-sparing approach using CDK4/6 inhibitor combined with aromatase inhibitor (minimum 5-year duration).

Primary Outcome Measures

Name	Time	Method
5-years Invasive disease free survival	5 years	5-year invasive disease-free survival (iDFS), defined as the time from randomization to the first occurrence of: local recurrence, distant metastasis, contralateral invasive breast cancer, death from any cause.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Approximately 5 years	OS is defined as the time from randomisation until the date of death due to any cause.
Safety including adverse events (AEs), severe adverse events (SAEs) and adverse events of special interest (AESI).	Up to approximately 3 years	Incidence of AEs, SAE, AESIs (interstitial lung disease, LVEF decrease), AEs resulting in study intervention interruption and discontinuation, etc.
Geriatric assessment (G-8)	Up to approximately 3 years	• Modified Geriatric-8 (G-8) screening tool
Clinical Frailty Scale	Up to approximately 3 years	Clinical Frailty Scale (CFS, version 2.0)