AiRuiKang (dalpiciclib)

Mechanistically, ENZ blocked AR-mediated transcriptional activation of MCM4, a critical component of the DNA helicase complex, thereby enhancing the effect of CDK4/6 inhibition on DNA replication and inducing a pronounced synergistic antitumor response. These results suggest that the ENZ-DAL combination is a promising therapeutic approach that warrants further clinical evaluation in CRPC patients.

P2, N=20, Not yet recruiting, Tang-Du Hospital

This article mainly reviews the mechanisms of action, clinical efficacy, and current application status of CDK4/6 inhibitors, including Palbociclib, Ribociclib, Abemaciclib, and the emerging Dalpiciclib. Strategies such as combining phosphoinositide 3-kinase (PI3K) inhibitors, immunotherapy, or new estrogen receptor (ER)-degrading agents are being actively explored for drug-resistant patients. The personalized precision therapy may become the core direction for optimizing the application of CDK4/6 inhibitors in the future, which will improve patients' quality of life.

P1, N=22, Completed, Beijing 302 Hospital | Trial completion date: Nov 2025 --> Mar 2026 | Trial primary completion date: Nov 2024 --> Dec 2025 | Not yet recruiting --> Completed

P2, N=716, Recruiting, Fudan University | Trial completion date: Sep 2028 --> Sep 2029 | Trial primary completion date: Dec 2026 --> Dec 2027

P1, N=46, Active, not recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting | N=90 --> 46 | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=57, Recruiting, Sun Yat-sen University

This is the larger real-world study to compare different CDK4/6 inhibitors in Chinese HR + /HER2 - ABC patients. Abemaciclib demonstrated a significant PFS advantage over palbociclib while maintaining a manageable safety profile, particularly benefiting biologically aggressive or treatment-resistant subgroups. These findings provide population-specific evidence to guide individualized CDK4/6 inhibitor selection and refine first-line treatment strategies for Chinese patients with HR + /HER2 - ABC.

P2, N=2000, Recruiting, Fujian Cancer Hospital

Subgroups including those without liver metastases, with secondary endocrine resistance, and receiving sequential CDK4/6i therapy appear to derive greater benefit. These findings support dalpiciclib as a viable cross-line therapeutic option, warranting further prospective validation.

Approved by the Ethics Committee of Peking Union Medical College Hospital (Approval number: K3629); registered at ClinicalTrials. gov (NCT05613270).

CDK4/6 inhibitors plus endocrine therapy significantly improved survival in hormone receptor-positive, HER2-negative advanced breast cancer. Benefits in progression-free survival and overall survival were consistent across major clinical subgroups. Although all agents improved progression-free survival, only ribociclib and abemaciclib showed statistically significant overall survival benefits, whereas palbociclib did not, and data for dalpiciclib remain immature. Further head-to-head comparisons and assessments of toxicity profiles, as well as patient-reported outcomes, are needed.