Abstract PS2-06-29: Chemotherapy-free neoadjuvant strategy in HR+/HER2- breast cancer: CDK4/6 inhibitors plus endocrine therapy show comparable efficacy to chemotherapy-sequenced approach

Abstract Background: The neoadjuvant treatment landscape for HR+/HER2- breast cancer is rapidly evolving. Although NACT demonstrates efficacy, its toxicity limits utility, whereas neoadjuvant endocrine therapy (ET) offers superior tolerability but inferior efficacy. Currently, in most Chinese centers, NACT remains the primary neoadjuvant approach for HR+/HER2- patients, with ET playing a supplementary role. However, the introduction of CDK4/6 inhibitors has transformed clinical practice, as their breakthrough efficacy in adjuvant therapy has brought revolutionary changes to disease management. The CORALLEEN trial demonstrated that preoperative CDK4/6 inhibitor combined with an aromatase inhibitor yields comparable efficacy to NACT. The WSG-ADAPT series of studies is also exploring whether CDK4/6 inhibitors can replace chemotherapy in intermediate-to-high risk HR+/HER2- early breast cancer. Nevertheless, whether patients can omit NACT remains controversial. This study aims to compare the objective response rate (ORR) between ET + CDK4/6 inhibitor alone and chemotherapy followed by ET + CDK4/6 inhibitor, while comprehensively evaluating treatment tolerability and adverse event profiles, to explore the feasibility of chemotherapy-sparing precision strategies. Methods: A total of 70 patients with HR+/HER2- breast cancer were enrolled across 11 tertiary hospitals. Of these, 45 received ET + CDK4/6 inhibitor (ribociclib [n=21], abemaciclib [n=16], dalpiciclib [n=7], palbociclib [n=1]). The remaining 25 patients underwent chemotherapy followed by ET + CDK4/6 inhibitor. ORR was defined as complete/partial radiologic response according to RECIST 1.1 criteria. For statistical analysis, the Mann-Whitney U test was used to analyze ranked data. The χ2 test or Fisher’s exact test was used to analyze categorical data. Logistic regression analysis was performed to identify significant factors for treatment response. All tests were two sided with significance level set at 0.05. All data cleaning and analysis were conducted using R statistical software (Version 4.5.0). Results: Baseline Characteristics and ORR Analysis by Treatment Groups: Median age of ET + CDK4/6 inhibitor vs chemotherapy-sequenced groups was 60 vs 55 years (P=0.029); Ki-67 was 20% vs 30% (P=0.023); other baseline characteristics (menopausal status (P =0.253), T stage (P =0.444), and N stage (P=0.721)) were balanced between treatment groups. The overall ORR was 63%, with higher responses observed in patients with Ki-67≤20% (68%) compared to those with Ki-67>20% (58%). The ET+CDK4/6i group achieved a 69% ORR (72% for Ki-67≤20% vs 63% for Ki-67>20%). No significant ORR difference between ET + CDK4/6 inhibitor (69%) and chemotherapy-sequenced groups (52%) (OR: 0.49, 95% CI: 0.18-1.34; P=0.164). The ribociclib-treated cohort achieved an ORR of 76% across all treatment strategies. Baseline Characteristics and ORR Analysis of Abemaciclib vs Ribociclib in non-Chemotherapy Patients: Median age of abemaciclib vs ribociclib groups was 61 vs 58 years (P=0.679); other baseline characteristics (menopausal status (P =1.000), T stage (P =0.641), N stage (P =0.191), or Ki-67 (P =0.709)) were balanced. Among non-chemotherapy patients, abemaciclib demonstrated comparable efficacy to ribociclib (ORR 62.5% vs 76.2%, OR: 1.82, 95% CI: 0.46-8.36; P=0.370). Conclusions: Primary ET + CDK4/6 inhibitor demonstrated comparable efficacy to chemotherapy-sequenced therapy in HR+/HER2- breast cancer, particularly in patients with low Ki-67. These results support the feasibility of chemotherapy-free neoadjuvant strategies for select HR+/HER2− patients, potentially minimizing chemotherapy-related toxicity without compromising treatment efficacy. Citation Format: A. zheng, Z. Dong, D. Song, F. Fang, J. Li, D. Zhang, G. Zhu, B. Guo, J. Li, Y. Zhao, N. Zhang, F. Jin, B. Chen. Chemotherapy-free neoadjuvant strategy in HR+/HER2- breast cancer: CDK4/6 inhibitors plus endocrine therapy show comparable efficacy to chemotherapy-sequenced approach [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-06-29.