Abstract PS3-10-13: Treatment outcomes of patients with early-stage breast cancer eligible, but not treated, with adjuvant ribociclib. a real-world cohort study

Abstract Background: Adjuvant CDK4/6 inhibitors, such as ribociclib and abemaciclib, have demonstrated significant disease-free survival (DFS) benefits in early-stage hormone receptor-positive (HR+)/HER2-negative breast cancer within randomized trials. However, real-world implementation remains limited, and outcomes for eligible-but-untreated populations are poorly characterized. This study evaluates treatment outcomes in patients retrospectively classified as eligible for adjuvant CDK4/6 inhibition under NATALEE criteria, all of whom were managed without such agents in routine practice. Methods: A retrospective cohort analysis was conducted using clinical data from patients with early-stage HR+/HER2-negative breast cancer. Eligibility for adjuvant ribociclib was assigned using trial-based criteria: stage IIA (high risk), IIB, or III disease as per the American Joint Committee on Cancer (AJCC) 8th edition. Kaplan-Meier methods and Cox proportional hazards models were employed to evaluate DFS and overall survival (OS), stratified by eligibility status. Results: Of the 2,730 patients included, 1,955 (71.6%) met the NATALEE eligibility criteria. Median (range) age was 50 (22-91) years and majority (n= 2,213, 81.1%) had invasive ductal carcinoma (IDC). A significant proportion of patients had high-risk disease with 1410 (51.6%) patients had pathologic node-positive disease, 602 (22.1%) had clinical T3 or T4, and 741 (27.1%) had grade 3 disease. Almost all patients were treated with adjuvant endocrine therapy with or without ovarian function suppression (OFS) with over half (n=1422, 52.1%) received an aromatase inhibitor (AI). However, none of the patients received adjuvant CDK4/6 inhibitors, allowing for real-world benchmarking of outcomes in a CDK4/6i-untreated setting. Across the cohort, patients eligible for CDK4/6 inhibitors had significantly worse 3-year DFS (85.2% [95% CI, 83.6%-86.8%]) compared to ineligible patients (95.1% [95% CI, 93.5%-96.6%]; HR = 2.75 [95% CI, 2.06-3.68]; p < 0.001). Stratified multivariable analysis revealed the following independent predictors of worse outcomes: Hazard Ratio (HR) for ER-negative vs. high-expression = 1.62 (95% CI: 1.10-2.39; p=0.015), high tumor grade (Grade 3): HR = 1.64 (95% CI: 1.20-2.25; p=0.002), clinical nodal involvement (cN+): HR= 1.27 (95% CI: 0.99-1.64; p=0.064), tumor size ≥cT3: HR = 2.23 (95% CI: 1.60-3.12; p<0.001). Although median OS was not reached in either group, separation of survival curves became apparent by 36 months and continued to widen thereafter, consistent with early relapse clustering in the higher-risk, untreated cohort. At 5 years, OS was 87.9% (95% CI, 86.4%-89.5%) in eligible patients compared with 95.9% (95% CI, 94.4%-97.4%) in the ineligible group. Together, these findings reveal a consistent and clinically meaningful survival gap between eligible-but-untreated patients and their lower-risk counterparts, highlighting the real-world impact of not receiving adjuvant CDK4/6-targeted therapy. Conclusions: A significant proportion of patients in this real-world cohort met criteria for adjuvant CDK4/6 inhibition but were not treated with these agents. These untreated, yet eligible individuals, experienced markedly worse survival outcomes compared to their ineligible counterparts. The data underscore a critical gap between evidence-based guidelines and clinical adoption. Closing this implementation gap could meaningfully impact recurrence rates and long-term survival in early-stage HR+ breast cancer. Citation Format: H. Abdel-Razeq, M. Horani, F. Tamimi, T. Al-Batsh, O. El Khatib, Y. Al-Masri, A. Ghanem, Q. Jawarneh, M. AL-yag'oub, A. Jaffal, R. Khader, S. Abdel-Razeq, A. Alanani, B. Sharaf, M. El-Atrash, M. Abunasser. Treatment outcomes of patients with early-stage breast cancer eligible, but not treated, with adjuvant ribociclib. a real-world cohort study [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 PS3-10-13.