Neoadjuvant stereotactic body radiotherapy plus dalpiciclib and exemestane for hormone receptor-positive, HER2-negative breast cancer.

e12604 Background: Despite cyclin dependent kinase 4/6 (CDK4/6) inhibitors having revolutionized treatment for advanced hormone receptor (HR)-positive, HER2-negative (HR+/HER2-) breast cancer, it still has limited efficacy in the neoadjuvant setting. Preclinical studies have indicated radiotherapy followed by CDK4/6 inhibitors can enhance antineoplastic effects. Stereotactic body radiotherapy (SBRT) is more effective than conventional fractionation. This MUKDEN 03 pilot study aimed to explore the efficacy and safety of a chemotherapy-free neoadjuvant regimen with SBRT followed by CDK4/6 inhibitors and endocrine therapy in patients with HR+/HER2- breast cancer. Methods: In this single-center, single-arm prospective study, treatment-naïve patients with unilateral invasive, pathologically confirmed HR+/HER2- breast cancer at stage II-III would be enrolled. Eligible patients received neoadjuvant SBRT (24Gy/3f) to breast target lesion followed by dalpiciclib (150mg daily for 3 weeks on and 1 week off) and exemestane (25mg daily) every 4 weeks for 6 cycles. Patients without menopause also received goserelin 3.6 mg every 4 weeks. The primary endpoint was the proportion of patients with residual cancer burden (RCB) score of 0-I. Key secondary endpoints included objective response rate (ORR), pathologic complete response (pCR), and safety. Results: Between November 2021 and August 2022, 12 enrolled patients completed the study treatment and surgery. The median age was 48.5 years (95% confidence interval [CI], 36-56) and half of them were premenopausal women. 5 (41.7%) patients had stage III disease. The results met the primary endpoint as the therapy resulted in RCB 0-I of 16.7% (2/12, 95% CI 3.5%-46.0%) with the ORR of 91.7% (11/12, 95% CI 62.5%-100%). 2 (16.7%, 95% CI 3.5%-46.0%) patients achieved pCR in the breast and axilla (ypT0/is ypN0). 3 (25.0%, 95% CI 8.3%-53.9%) patients reached pCR in the breast (ypT0/is). The most common grade 3 adverse events (AEs) were neutropenia (8 [66.7%]) and leukopenia (3 [25%]). No patient experienced grade 4-5 AE or death. There was no patient with radiation-related dermatitis and skin hyperpigmentation. Conclusions: Neoadjuvant SBRT followed by dalpiciclib and exemestane seems effective and tolerable, which may offer an alternative for patients with HR+/HER2- breast cancer. The results warranted further validation. Clinical trial information: NCT05132790 .