AiRuiKang (dalpiciclib)

Entecavir antiviral therapy led to suppressed viral replication and improved liver function during follow-up. This case emphasizes the need for HBV screening and close monitoring of viral markers/liver function in asymptomatic HBV carriers receiving dalpiciclib, as early antiviral intervention prevents severe liver complications. It also highlights the importance of clinical pharmacist-led medication follow-up management for outpatients receiving targeted anticancer therapy to avoid oversight of comorbidities and associated prophylactic treatment.

Preclinical studies have demonstrated synergistic antitumor activity when CDK4/6 inhibitors are combined with trastuzumab, pertuzumab, or newer HER2-targeted agents across multiple HER2+ breast cancer models. In the metastatic setting, phase II trials including MonarcHER and PATRICIA II have shown encouraging efficacy signals, while the phase III PATINA trial demonstrated a clinically meaningful 15.2-month progression-free survival benefit with palbociclib plus anti-HER2 therapy and endocrine therapy...Despite these advances, key challenges remain including the identification of predictive biomarkers, optimal treatment sequencing, and the integration of emerging HER2-targeted agents such as trastuzumab deruxtecan. Novel CDK4/6 inhibitors including dalpiciclib and next-generation agents are expanding therapeutic options, while combination strategies incorporating CDK7 inhibition represent future therapeutic frontiers. The evolving landscape of HER2+/HR+ breast cancer treatment increasingly emphasizes precision medicine approaches that leverage cell cycle control mechanisms to overcome resistance and improve patient outcomes across all disease stages.

P3, N=912, Recruiting, Shandong Suncadia Medicine Co., Ltd. | Not yet recruiting --> Recruiting | Initiation date: Dec 2026 --> Mar 2026

P2, N=60, Recruiting, Hebei Medical University Fourth Hospital

P2, N=100, Enrolling by invitation, Peking University | Not yet recruiting --> Enrolling by invitation

P3, N=258, Recruiting, Fujian Cancer Hospital

P3, N=2288, Not yet recruiting, Fudan University

This triplet regimen demonstrated modest clinical activity in HR+/HER2- early BC, with the safety profile of this regimen remains a concern and warrants particular attention in clinical practice.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i; palbociclib, ribociclib, abemaciclib, dalpiciclib) combined with endocrine therapy (ET) were a major advance in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) worldwide...However, clinical development of CDK4/6i in HER2+ MBC slowed, given the advent of highly effective tyrosine-kinase inhibitors (TKIs) (i.e., tucatinib) and antibody-drug conjugates (ADCs) (i.e., trastuzumab deruxtecan), which currently dominate the treatment armamentarium...Subsequently, the phase III PATINA trial (which included patients with 1L HR+HER2+ MBC, treated with palbociclib vs. placebo with maintenance ET+ H[P]) noted a striking PFS improvement of >15 months in the palbociclib arm, renewing interest in CDK4/6i-based treatments for HR+HER2+ MBC. Herein, we review the development of CDK4/6i in HER2+ BC, discussing current challenges and potential future directions.

The most commonly used CDK4/6i were abemaciclib (33.39%), dalpiciclib (28.98%), palbociclib (25.76%), and ribociclib (10.85%). CDK4/6i demonstrates favorable real-world efficacy in HR+/HER2- MBC patients in central China, particularly in the first-line setting. Several clinical factors may aid in treatment selection and risk stratification.

P2/3, N=119, Completed, Tianjin Medical University Cancer Institute and Hospital | Recruiting --> Completed | Trial completion date: Sep 2026 --> Sep 2025

P=N/A, N=103, Recruiting, RenJi Hospital | Trial primary completion date: Dec 2025 --> Jan 2027