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.

Abstract

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.