Adding a CDK4/6 blocker to hormone treatment after surgery for high-risk HR+/HER2+ early breast cancer

A Study on the Efficacy and Safety of CDK4/6 Inhibitors Combined With Standard Adjuvant Endocrine Therapy in High-Risk, HR+/HER2+ Early Breast Cancer Patients Who Have Completed Adjuvant Anti-HER2 Targeted Therapy"

This trial tests whether adding a CDK4/6 inhibitor to standard hormone therapy after surgery helps women aged 18–70 with high-risk HR+/HER2+ early breast cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1903 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: trastuzumab
• Locations: 1 site (Shanghai)
• Trial ID: NCT07019363 on ClinicalTrials.gov

What this trial studies

This is a prospective, open-label, randomized Phase III trial comparing standard adjuvant endocrine therapy alone versus endocrine therapy combined with a CDK4/6 inhibitor. It enrolls women 18–70 with histologically confirmed HR+/HER2+ early breast cancer at high risk (≥pN1 after surgery, residual disease after neoadjuvant therapy, or pre-treatment cT4/N3), within one year of completing anti-HER2 therapy. Participants receive standard endocrine options (tamoxifen or anastrozole/letrozole/exemestane) with or without an oral CDK4/6 inhibitor and are followed for safety and cancer outcomes. The trial is designed to see if adding CDK4/6 inhibition reduces recurrence compared with endocrine therapy alone.

Who should consider this trial

Good fit: Women aged 18–70 with ECOG 0–1 and histologically confirmed HR+/HER2+ early breast cancer who are high risk by pathology or pre-treatment staging and who completed anti-HER2 therapy within the past year are ideal candidates.

Not a fit: Patients with low-risk disease, ER/PR under 10%, HER2-negative tumors, poor performance status, contraindications to CDK4/6 inhibitors, or inability to attend the Shanghai site are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, adding a CDK4/6 inhibitor could lower the risk of recurrence and improve long-term outcomes for high-risk HR+/HER2+ early breast cancer patients.

How similar studies have performed: CDK4/6 inhibitors have shown clear benefits in advanced HR+ breast cancer and some triple-positive advanced cases, but adjuvant use in early HR+/HER2+ disease remains experimental and is still being tested.

Eligibility criteria

Inclusion Criteria:

1. Females aged ≥18 and ≤70 years.
2. ECOG systemic status grade 0 to 1.
3. Histologically confirmed invasive HR+/HER2+ breast cancer (Specific definition: breast cancer patients whose estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) are all determined to be positive by pathologic testing. Specifically: ER positive: IHC\>10%, PR positive: IHC\>10%, HER2 positive: IHC+++ or IHC++ but amplified by FISH.
4. Early-stage breast cancer after radical mastectomy with postoperative pathology consistent with TNM staging of ≥pN1 ; or postoperative pathology suggestive of non-pCR after neoadjuvant therapy; or postoperative pathology suggestive of pCR after neoadjuvant therapy but with clinical staging consistent with cT4 or N3 before neoadjuvant therapy
5. Within 1 year of completion of adjuvant anti-HER2 targeted therapy: anti-HER2 targeted therapy includes trastuzumab-based therapy, and/or T-DM1 therapy, and/or TKI therapy.
6. The function of major organs is basically normal, and the following conditions are met: ① The criteria for routine blood tests need to be met: HB ≥ 90g/L (no blood transfusion within 14 days); ANC ≥ 1.5 × 109/L; PLT ≥ 75 × 109/L; ② The biochemical tests need to be met as follows: TBIL ≤ 1.5 × ULN (the upper limit of normal value); ALT and AST ≤ 3 × ULN; serum Cr ≤ 1 × ULN, and endogenous creatinine clearance \> 50 ml/min (Cockcroft-Gault formula).
7. Female subjects of childbearing potential are required to use a medically approved form of contraception during study treatment, and for at least 3 months after the last dose of study drug.
8. Subjects voluntarily enrolled in the study, signed an informed consent form, were compliant, and cooperated with follow-up visits.

Exclusion Criteria:

1. Bilateral breast cancer;
2. Metastasis to any site;
3. Taking food or medications that are strong inhibitors or inducers of CYP3/4.

   1. Strong inhibitors of CYP3/4 include: boceprevir, clarithromycin, konifactam, delavirdine, indinavir, itraconazole, ketoconazole, ritonavir, mibefradil, miconazole, fazodone, nelfinavir, propoxiconazole, ritonavir, saquinavir, naloxone, telaprevir, telithromycin, voriconazole, grapefruit, grapefruit juice, or grapefruit containing foods.
   2. Strong inducers of CYP3/4 including carbamazepine, phenytoin, pramipexole, rifampin, and St. John's wort.
4. History of clinically significant or uncontrolled cardiac disease including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia;
5. other malignancy within the previous 5 years, excluding cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin;
6. Pregnant or lactating women, women of childbearing age who are unable to use effective contraception;
7. Patients who are concurrently enrolled in other clinical trials;
8. severe or uncontrolled infection;
9. Patients with known active HBV or HCV infection or Hepatitis B DNA ≥500, or chronic stage with abnormal liver function;
10. Those with a history of psychotropic substance abuse that cannot be stopped or those with psychiatric disorders;
11. Patients who, in the judgment of the investigator, are not suitable for participation in this study.

Where this trial is running

Shanghai

• Fudan cancer center — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: zhimin shao — Fudan University
• Study coordinator: Zhimin Shao, MD, PhD

Conditions Breast Cancer; Adjuvant Therapy