Efficacy and safety of neoadjuvant stereotactic body radiation therapy plus dalpiciclib and exemestane for hormone receptor-positive, HER2-negative breast cancer: A prospective pilot study

• DOI: 10.7554/elife.101583.2
• Publication Date: 2025-05-15T15:30:14Z
• Authors: Yu Zhang; Shuo Cao; Nan Niu; Huilian Shan; Jinqi Xue; Guanglei Chen; Yongqing Xu; Jianqiao Yin; Chao Liu; Lisha Sun; Xiaofan Jiang; Meiyue Tang; Qianshi Xu; Mingxuan Jia; Xu Zhang; Zhenyong Zhang; Qingfu Zhang; Jianfei Wang; Ailin Li; Yongliang Yang; Caigang Liu
• Keywords: Exemestane

Abstract Background Both neoadjuvant chemotherapy and endocrine therapy only result in trivial pathological complete response rates moderate objective (ORR) hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer, more promising alternatives are urgently needed. With proven synergistic effect of cyclin dependent kinase 4/6 (CDK4/6) inhibitor radiotherapy preclinical studies, this pilot study aimed to explore the efficacy safety stereotactic body radiation (SBRT) followed by dalpiciclib exemestane HR-positive, HER2-negative cancer. Methods This was a single-arm, non-controlled prospective study. Treatment-naïve patients with unilateral cancer received (24Gy/3F) for 6 cycles. The primary endpoint proportion residual burden (RCB) score 0-I. Key secondary endpoints included ORR, breast-conservation rate, biomarker analysis, safety. Results All 12 enrolled completed treatment surgery. Two (16.7%) them achieved RCB 0-I ORR 91.7% (11/12). Analyses tumor specimens showed significant increase infiltrating T cells rather than alteration PD-L1 positive immune cells. most common grade 3 adverse events (AEs) were neutropenia (66.7%) leukopenia (25.0%), but no 4-5 AE or death occurred. Conclusions Our results suggested SBRT effective tolerable, provides novel insights HR+/HER2-breast which may be considered as feasible option