CDK4/6 Inhibitor Intensification and Chemotherapy De-Escalation for Early-stage Luminal-HER2 Breast Cancer

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer
• Interventions: Drug: CDK 4/6 inhibitor combined therapy (omit chemo); Drug: standard of care

• Registration Number: NCT07213206
• Lead Sponsor: Fudan University

Brief Summary

The investigators designed a phase III clinical trial involving hormone receptor-positive and HER2-positive stage I breast cancer patients. This trial aims to evaluate the efficacy and safety of a treatment regimen combining CDK4/6 inhibitors, endocrine therapy, and anti-HER2 therapy compared with the traditional approach of chemotherapy combined with anti-HER2 therapy.

Detailed Description

For patients with hormone receptor-positive and HER2-positive breast cancer, the NCCN guidelines recommend that those with tumors larger than 1 cm or positive lymph nodes should receive standard adjuvant therapy comprising chemotherapy combined with targeted and endocrine therapy. In contrast, for patients with tumors smaller than 1 cm and negative lymph nodes, endocrine therapy alone or in combination with targeted therapy and chemotherapy may be considered. Therefore, in patients with stage I hormone receptor-positive and HER2-positive breast cancer, it remains unclear whether chemotherapy can be omitted by intensifying endocrine therapy through the addition of CDK4/6 inhibitors, particularly considering the intrinsic therapeutic efficacy of endocrine agents and their potential synergistic interaction with anti-HER2 therapy. To further minimize treatment-related toxicity and identify the optimal adjuvant treatment strategy for patients with HER2-positive stage I breast cancer, the investigators designed a phase III clinical trial involving hormone receptor-positive and HER2-positive stage I breast cancer patients. This trial aims to evaluate the efficacy and safety of a treatment regimen combining CDK4/6 inhibitors, endocrine therapy, and anti-HER2 therapy compared with the traditional approach of chemotherapy combined with anti-HER2 therapy.

Study Timeline

• Study First Submitted: 2025-07-18
• Status Verified: 2025-10
• Study First Submitted QC: 2025-10-01
• Last Update Submitted: 2025-10-01
• Study Start: 2025-10-07
• Study First Posted: 2025-10-08
• Last Update Posted: 2025-10-08
• Primary Completion: 2032-09-01
• Study Completion: 2035-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 1500

Inclusion Criteria

1. Female patients aged between 18 and 75 years;
2. Unilateral invasive carcinoma confirmed by histopathological examination;
3. Postoperative pathological stage I early breast cancer: histologically confirmed invasive carcinoma with a maximum tumor diameter not exceeding 2 cm and no lymph node metastasis (N0);
4. Estrogen receptor (ER) expression ≥ 50%;
5. Immunohistochemical and molecular pathology must meet one of the following criteria: HER-2 overexpression (3+) or HER-2 (0-2+) with gene amplification confirmed by fluorescence in situ hybridization (FISH);
6. Histological grade 1-2 or selected grade 3 tumors with at least one of the following additional features: PAM50 or HER2-based subtyping indicating luminal phenotype , or tumor size ≤ 1 cm );
7. Adequate major organ function, defined as:

(1) Hematologic parameters: hemoglobin (HB) ≥ 90 g/L (without blood transfusion within 14 days), absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count (PLT) ≥ 100 × 10⁹/L; (2) Biochemical parameters: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, serum creatinine (Cr) ≤ 1 × ULN, and calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault formula; 8) Cardiac function preserved with left ventricular ejection fraction (LVEF) > 50%; 9) Willing to participate in the study, with signed informed consent, good compliance, and willingness to comply with follow-up requirements.

Exclusion Criteria

1. Tumors with a maximum diameter exceeding 2 cm and/or presence of positive axillary lymph nodes;
2. HER2-negative status defined as HER2- or HER2+ by immunohistochemistry; or HER2 2+ by immunohistochemistry without gene amplification confirmed by fluorescence in situ hybridization (FISH);
3. Patients who have previously received neoadjuvant therapy or any form of systemic or non-surgical local treatment prior to enrollment, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy;
4. History of other malignant tumors, excluding cured basal cell carcinoma of the skin and cervical carcinoma in situ;
5. Has metastatic (Stage 4) breast cancer;
6. Pregnant or lactating women, as well as women of childbearing potential who are unable to use effective contraception;
7. Patients currently enrolled in other clinical trials;
8. Severe organ dysfunction involving the cardiovascular, pulmonary, hepatic, or renal systems, including left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiography; history of severe cardiovascular or cerebrovascular events within 6 months prior to enrollment (e.g., unstable angina, chronic heart failure, uncontrolled hypertension > 150/90 mmHg, myocardial infarction, or stroke); patients with poorly controlled diabetes mellitus; patients with severe or uncontrolled hypertension;
9. Active severe or uncontrolled infections;
10. Patients with a history of substance abuse involving psychotropic drugs with ongoing dependency, or a documented history of psychiatric disorders that may interfere with study compliance;
11. Patients deemed unsuitable for participation by the principal investigator or designated study physician.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CDK 4/6 inhibitor combined therapy (omit chemo)	CDK 4/6 inhibitor combined therapy (omit chemo)	CDK4/6 inhibitor for two years combined with endocrine therapy for five years and Trastuzumab(without chemo) for one year
standard of care	standard of care	four cycles of docetaxel and cyclophosphamide or four cycles of weekly paclitaxel combined with Trastuzumab for one year

Primary Outcome Measures

Name	Time	Method
iDFS	3 years	invasive disease-free survival

Secondary Outcome Measures

Name	Time	Method
RFS	3 years	recurrence-free survival
DRFS	3 years	distant recurrence-free survival
OS	3 years	overall survival
adverse effects	3 years	adverse effects according to CTCAE 5.0