Zhang Yu, Cao Shuo, Niu Nan, Shan Huilian, Xue Jinqi, Chen Guanglei, Xu Yongqing, Yin Jianqiao, Liu Chao, Sun Lisha, Jiang Xiaofan, Tang Meiyue, Xu Qianshi, Jia Mingxuan, Zhang Xu, Zhang Zhenyong, Zhang Qingfu, Wang Jianfei, Li Ailin, Yang Yongliang, Liu Caigang
Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, China.
Elife. 2025 Jul 28;14:RP101583. doi: 10.7554/eLife.101583.
Both neoadjuvant chemotherapy and endocrine therapy only result in trivial pathological complete response rates and moderate objective response rates (ORR) in 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 and radiotherapy in preclinical studies, this pilot study aimed to explore the efficacy and safety of neoadjuvant stereotactic body radiation therapy (SBRT) followed by dalpiciclib and exemestane in HR-positive, HER2-negative breast cancer.
This was a single-arm, non-controlled prospective pilot study. Treatment-naive patients with unilateral HR-positive, HER2-negative breast cancer received neoadjuvant radiotherapy (24 Gy/3 F) followed by dalpiciclib and exemestane for six cycles. The primary endpoint was the proportion of patients with residual cancer burden (RCB) score of 0-I. Key secondary endpoints included ORR, breast-conservation rate, biomarker analysis, and safety.
All 12 enrolled patients completed the study treatment and surgery. Two (16.7%) of them achieved the RCB 0-I with the ORR of 91.7% (11/12). Analyses of tumor specimens showed significant increase of infiltrating T cells rather than alteration of PD-L1 positive immune cells. The most common grade 3 adverse events (AEs) were neutropenia (66.7%) and leukopenia (25.0%), but no grade 4-5 AE or death occurred.
Our results suggested neoadjuvant SBRT followed by dalpiciclib and exemestane is effective and tolerable and provides novel insights for the neoadjuvant treatment of HR+/HER2- breast cancer, which may be considered as a feasible option for patients with HR-positive, HER2-negative breast cancer.
None.
ClinicalTrials.gov: NCT05132790.
新辅助化疗和内分泌治疗在激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性乳腺癌中仅产生微不足道的病理完全缓解率和中等的客观缓解率（ORR），迫切需要更有前景的替代方案。鉴于临床前研究已证实细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂与放疗具有协同作用，本前瞻性试点研究旨在探索新辅助立体定向体部放疗（SBRT）联合达尔西利和依西美坦治疗HR阳性、HER2阴性乳腺癌的疗效和安全性。
这是一项单臂、非对照的前瞻性试点研究。未接受过治疗的单侧HR阳性、HER2阴性乳腺癌患者接受新辅助放疗（24 Gy/3次分割），随后接受达尔西利和依西美坦治疗六个周期。主要终点是残留癌负担（RCB）评分为0-I的患者比例。关键次要终点包括ORR、保乳率、生物标志物分析和安全性。
所有12例入组患者均完成了研究治疗和手术。其中2例（16.7%）达到RCB 0-I，ORR为91.7%（11/12）。肿瘤标本分析显示浸润性T细胞显著增加，而非PD-L1阳性免疫细胞发生改变。最常见的3级不良事件（AE）是中性粒细胞减少（66.7%）和白细胞减少（25.0%），但未发生4-5级AE或死亡。
我们的结果表明，新辅助SBRT联合达尔西利和依西美坦是有效且可耐受的，并为HR+/HER2-乳腺癌的新辅助治疗提供了新见解，这可能被视为HR阳性、HER2阴性乳腺癌患者的一种可行选择。
无。
ClinicalTrials.gov：NCT05132790。
