Chemotherapy-free neoadjuvant strategy in HR+/HER2− early breast cancer: Efficacy of CDK4/6 inhibitors plus endocrine therapy compared to chemotherapy-sequenced approach.

Abstract

e12671 Background: In HR+/HER2- breast cancer (BC), neoadjuvant chemotherapy (NACT) remains a standard in many regions despite low pathological complete response (pCR) rates (7.5%–16.2%) and significant toxicity. The emergence of CDK4/6 inhibitors (CDK4/6i) has transformed management, with trials like CORALLEEN and WSG-ADAPT suggesting that neoadjuvant endocrine therapy (ET) plus CDK4/6i may offer comparable efficacy to NACT with improved tolerability. This study evaluates the feasibility of chemotherapy-sparing strategies by comparing the objective response rate (ORR) and safety of neoadjuvant ET+CDK4/6i versus NACT followed by ET+CDK4/6i in a real-world setting. Methods: We retrospectively analyzed 63 patients (aged 18–70 years) with HR+/HER2- BC across 11 tertiary hospitals in China. Patients were divided into two groups: those receiving neoadjuvant ET+CDK4/6i (n = 38; ribociclib, abemaciclib, dalpiciclib, or palbociclib) and those receiving NACT followed by ET+CDK4/6i (n = 25). ORR was defined by RECIST 1.1. Statistical analyses included Mann-Whitney U,X 2 , or Fisher’s exact tests, and logistic regression. Results: Baseline characteristics (age, Ki-67, T/N stage, and menopausal status) were well-balanced between groups ( P > 0.05). The overall ORR was 62%, with higher responses observed in patients with Ki-67≤20% (67%) compared to those with Ki-67 > 20% (58%). No significant difference in ORR was observed between the ET+CDK4/6i group (68%) and the chemo-sequenced group (52%) (OR: 0.41, 95% CI: 0.10–1.56; P = 0.200). In the Ki-67 > 20% subgroup, ET+CDK4/6i maintained a comparable ORR to the chemo-sequenced approach (63% vs. 53%, OR: 0.91, 95% CI: 0.64-1.29; P = 0.683). Among non-chemotherapy patients, ribociclib and abemaciclib showed similar efficacy (ORR 71% vs. 69%, OR: 1.07, 95% CI: 0.21-5.21; P = 0.936), while the dalpiciclib cohort achieved an ORR of 25% (n = 4, P = 0.121). Treatment was generally well-tolerated across cohorts. Conclusions: Neoadjuvant ET plus CDK4/6i achieves short-term ORR comparable to chemotherapy-sequenced regimens in HR+/HER2- early BC, even in patients with high Ki-67. These findings support the feasibility of chemotherapy-free neoadjuvant strategies for clinically selected patients, potentially mitigating toxicity without compromising initial treatment response.