NCT07366112

CDK4/6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment

CDK4/6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment of Breast Cancer: ctDNA-Guided Personalized Therapy

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 158 (estimated)
• Sponsor: Peking University People's Hospital · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Exploring the dynamics of ctDNA following neoadjuvant therapy with CDK4/6 inhibitors combined with endocrine treatment, and its potential to guide de-escalation of adjuvant chemotherapy

Detailed description

Breast cancer remains a leading cause of cancer-related morbidity and mortality globally, with hormone receptor-positive (HR+), HER2-negative (HER2-) subtypes accounting for approximately 70% of cases. While adjuvant chemotherapy is standard for high-risk early-stage HR+/HER2- breast cancer, it carries significant toxicity, and many patients may not derive clinical benefit. Emerging evidence suggests that circulating tumor DNA (ctDNA)-a minimally invasive biomarker reflecting residual disease-may guide personalized treatment de-escalation. Preclinical and clinical studies demonstrate that ctDNA dynamics correlate with tumor burden and prognosis. In HR+ breast cancer, ctDNA clearance after neoadjuvant therapy is associated with improved survival, while persistent ctDNA post-treatment predicts recurrence. CDK4/6 inhibitors, such as Dalpiciclib, have revolutionized advanced HR+/HER2- breast cancer management by enhancing endocrine therapy efficacy. However, their role in early-stage disease, particularly in a ctDNA-guided de-escalation strategy, remains underexplored. This study addresses this gap by evaluating whether ctDNA-driven decision-making can safely reduce chemotherapy use while maintaining clinical outcomes. Study Objectives Primary Objectives: Assess ctDNA clearance rate (defined as conversion from detectable to undetectable ctDNA) after 4 cycles of neoadjuvant CDK4/6i + endocrine therapy. Secondary Objectives Evaluate 3-year event-free survival (EFS), where events include local/distant recurrence, secondary malignancies, or death. Compare safety profiles of CDK4/6i + endocrine therapy versus chemotherapy. Evaluate tumor response metrics: Pathological complete response (pCR) and residual cancer burden (RCB 0-1). Complete cell cycle arrest (CCCA; Ki67 ≤2.7%). Assess objective response rate (ORR) by RECIST 1.1. Exploratory Objectives Correlate ctDNA clearance with long-term outcomes (e.g., EFS, overall survival). Study Design All patients received 4 cycles of neoadjuvant CDK4/6i + endocrine therapy. Post-Surgery Treatment： ctDNA-negative post-neoadjuvant: Continue CDK4/6i + endocrine therapy ctDNA-positive post-neoadjuvant: Optional adjuvant chemotherapy followed by CDK4/6i + endocrine therapy.

Conditions

• Hormone Receptor-Positive Breast Cancer
• High-risk Breast Cancer
• Early-Stage Breast Cancer
• HER2-negative Breast Cancer
• ctDNA Monitoring

Interventions

Type	Name	Description
DRUG	CDK4/6 inhibitor with endocrine therapy	CDK4/6 inhibitor with endocrine therapy for neoadjuvent therapy

Timeline

• Start date: 2026-02-01
• Primary completion: 2028-01-01
• Completion: 2029-12-31
• First posted: 2026-01-26
• Last updated: 2026-01-26