Journal Article

Efficacy, Safety, and Biomarkers of Neoadjuvant Dalpiciclib (CDK4/6 inhibitor) plus Aromatase Inhibitors in Operable HER2‐Negative Luminal B Breast Cancer: A Prospective, Single‐Center, Single‐Arm, Phase II Trial (DANCER)

Chen, Huihui, Wu, Shijie, Ma, Ting, Shen, Yong, Zhang, Zhiyun, Zhang, Jiao, Hong, Hui, Guo, Xianan, Wang, Hui, Pan, Liqiang, Chen, Yiding, Hu, Yue, Ma, Mindi, Qian, Wei, Zhou, Yunxiang, Mao, Weikang, Wang, Ze, Fu, Jun, Pan, Chi, Huang, Fengbo, Tao, Siqi, Shen, Lu

2025

Overview

Dalpiciclib, a cyclin‐dependent kinase 4/6 (CDK4/6) inhibitor, has demonstrated significant clinical activity and manageable safety in advanced luminal breast cancer, yet its neoadjuvant value remains unestablished. The single‐arm, phase II DANCER trial (NCT05640778) is the first to evaluate circulating tumor DNA (ctDNA)‐guided neoadjuvant CDK4/6 inhibitor therapy in patients with operable human epidermal growth factor receptor 2 (HER2)‐negative luminal B breast cancer, a subtype with poor chemotherapy response and unmet neoadjuvant needs. Thirty patients received dalpiciclib plus aromatase inhibitors (DAL‐AI) with ctDNA monitoring and multiomics profiling. At week 2, 26 (86.7%) patients achieved complete cell cycle arrest (primary endpoint). By surgery, 60.0% had partial response; breast pathological complete response and residual cancer burden 0–I rates were 6.7 and 3.3%, respectively. Treatment was well tolerated, with the most common grade ≥3 adverse events being neutropenia and leukopenia. Candidate predictive biomarkers included ctDNA clearance, GSTM1 copy number, MammaPrint index, plasma CCL4/CCL19 levels, and tissue pRb/CDK4 expression. A novel baseline response index combining CCL4 and pRb showed excellent predictive performance and stratified patients by likelihood of clinical benefit, with ctDNA dynamics further refining stratification. These findings support DAL‐AI as a promising neoadjuvant option and highlight the value of biomarker‐guided strategies for treatment optimization. DANCER (NCT05640778) was a circulating tumor DNA (ctDNA)‐directed, single‐arm, phase II trial investigating the clinical activity of dalpiciclib combined with aromatase inhibitors as a neoadjuvant regimen for operable human epidermal growth factor receptor 2 (HER2)‐negative luminal B breast cancer. Although a high complete cell cycle arrest (CCCA) rate (primary endpoint) of 86.7% (26 out of 30) was achieved at 2 weeks, some patients showed suboptimal clinical responses after neoadjuvant therapy. Comprehensive multiomics biomarker analysis revealed that patients with early ctDNA clearance, MammaPrint low‐risk status, GSTM1 deletion, increased tissue pRb/CDK4 expression, and higher plasma CCL4/CCL19 levels are likely to benefit more from neoadjuvant dalpiciclib therapy. The lower right (BIOMARKERS) panel was created in BioRender. Zhou, Y. (2025) https://BioRender.com/ax0bxdu.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: biomarker / Biomarkers / Breast cancer / Cancer therapies / CDK4/6 inhibitor / Cell cycle / circulating tumor DNA / luminal B breast cancer / neoadjuvant / Olink proteomics