Abstract P3-05-26: Efficacy of first-line CDK4/6 inhibitors stratified by ER, PR, HER2 expression levels and Ki-67 in hormone receptor-positive, HER2 negative metastatic breast cancer: Real-world outcomes

Abstract Introduction: Cyclin-Dependent kinase 4 and 6 (CDK4/6) inhibitors (palbociclib/ abemaciclib/ ribociclib) combined with endocrine therapy (ET) as first-line treatment has significantly improved progression-free survival (PFS) in hormone receptor-positive (HR+), HER2 negative (HER2-) metastatic breast cancer, with ribociclib also showing statistically significant improvement in overall survival (OS) in phase III studies. However, these phase III studies have not assessed efficacy differences based on estrogen receptor (ER), progesterone receptor (PR), HER2 receptor, or Ki-67 levels. Our study aims to evaluate the impact of ER, PR, HER-2, and Ki-67 on PFS and OS in metastatic HR+, HER2- breast cancer treated with CDK4/6 inhibitor and ET in their first line. Methods: We conducted a retrospective study of 146 patients with metastatic HR+ HER2- breast cancer treated with first-line CDK4/6 inhibitor and ET at our institution. We have recorded ER, PR, HER2, and Ki-67 expression levels from their first metastatic site biopsy, along with age, gender, ethnicity, menopausal status, location of metastatic sites, date of initiation of CDK 4/6 inhibitor, and date of progression or death. The primary endpoints were PFS and OS stratified by ER (≤50% vs >50%), PR (≤50% vs>50%), HER2 (0 or 1+ vs 2+ on IHC) and Ki67 (≤20% vs >20%) levels. Survival distributions were estimated using the Kaplan-Meier method, and independent group t-tests were used to compare the difference in median between two groups. We also calculated OS and PFS using restricted mean survival time (RMST) which is the area under the survival curve upto a specific time. Results: The ≤ 50% ER group had a median time for PFS of 15.5 months, RMST for PFS of 29 months, median OS of 47 months, RMST for OS of 48.3 months; whereas the > 50% group had significantly longer median PFS of 49 months, RMST for PFS of 47.3 months, median OS of 80.3 months, RMST for OS of 64 months (p=0.002, 0.016, 0.006, 0.05 respectively). The ≤ 50% PR group had a median PFS of 27.3 months, RMST for PFS of 60.5 months, median OS of 63.7 months, RMST for OS of 93.2 months; while the >50% PR group had significantly longer median PFS of 77.3 months, RMST for PFS of 99.4 months, median OS of 116.7 months, RMST for OS of 133.9 months (p= 0.013, 0.024, 0.014, 0.039 respectively). The 0 or 1+ HER2 IHC group had a median PFS of 45.4 months, RMST for PFS of 53.9 months, median OS of 71 months, RMST for OS of 69.9 months; while the 2+ HER2 IHC group had a median PFS of 49 months, RMST for PFS of 48.4 months, median OS of 77 months, RMST for OS of 71.4 months (p=0.25, 0.50, 0.74, 0.86 respectively). The ≤ 20% Ki-67 group had a median PFS of 75.9 months, RMST for PFS of 96.3 months, median OS of 225.3 months, RMST for OS of 140.9 months, while the >20% Ki-67 group had a significantly shorter median PFS of 37.3 months, RMST for PFS of 56.4 months, median OS of 68.8 months, RMST for OS of 82.6 months (p=0.005, 0.006, 0.006, <0.001 respectively). Conclusion: Higher ER and PR levels were linked to significantly longer PFS and OS, while higher Ki-67 levels were associated with significantly shorter PFS and OS. HER2 IHC levels had no significant impact on PFS and OS. Our study highlights ER, PR and Ki-67 levels as predictive factors for HR+ HER2- metastatic breast cancer patients on CDK4/6 inhibitors. Larger studies are warranted to confirm the utility of these markers as predictive factors for CDK4/6 inhibitor therapy across different treatment lines. Citation Format: Maya Gogtay, Olivia L. Makos, Lina Elsayed, Robin R. High, Meghana Kesireddy. Efficacy of first-line CDK4/6 inhibitors stratified by ER, PR, HER2 expression levels and Ki-67 in hormone receptor-positive, HER2 negative metastatic breast cancer: Real-world outcomes [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-05-26.