Abstract PO1-17-12: The impact of treatment sequence of CDK4/6 inhibitor therapy on Metastatic Breast Cancer treatment outcomes in Real-World practice in U.S
Authors: Kimmick Gretchen , PIlehvari Asal , You Wen , Bonilla Gloribel , Anderson Roger 
Published: May 2024

Abstract
Background A retrospective study to describe the actual benefit of treatment sequence with Endocrine Therapy (ET) plus cyclin D/cyclin-dependent kinases 4 and 6 (CDK4/6) therapy including as 1st-line and 2nd -line treatment for Metastatic breast cancer (MBC) patients with hormone receptor positive (HR+) and HER2 negative. We examined the extent that treatment sequence of CDK4/6 inhibitor therapy is associated with progression-free survival, and overall survival under real-world conditions. Methods This study used the nationwide electronic health record-derived-Flatiron Health de-identified database to estimate the real-world progression-free survival (rwPFS) and overall survival (rwOS) of MBC patients under different treatment sequence of CDK4/6 inhibitors. A total of 2,771 patients with ≥ 3 months of follow-up received either CDK4/6 inhibitor plus ET in the first-line setting (n=2,170) or ET alone in the first-line and CDK4/6 inhibitor plus ET in the second-line setting (n=601) between February 3, 2015, and November 02, 2021. We performed inverse probability weighting (IPW) to balance the baseline demographic and clinical characteristics between patients in the two groups. Kaplan-Meier method and Cox proportional hazards were used to test for an association of CDK4/6 treatment line sequence on PFS as the primary outcome and OS as the secondary outcome, adjusting for patient characteristics (e.g., age, race, comorbidities, ECOG value, Tumor site, and health insurance). Results Median follow-up was 25.6 months (interquartile range [IQR], 12.7–41.3) for the group with CDK4/6 inhibitor plus ET in first-line treatment and 33.1 months (IQR, 18.1–50.4) in those taking ET alone in first-line and CDK4/6 inhibitor plus ET in the second-line treatment. CDK4/6 inhibitor combination with ET as the first-line treatment was associated with significantly longer median rwPFS compared to receiving ET alone on first line and CDK4/6 inhibitor plus ET in the second line (28.0 vs 13.1 months; hazard ratio [HR], 0.40; 95% CI, 0.35–0.44; P &lt; 0.0001). Median rwOS was 52 months for the group with first line CDK4/6 inhibitor plus ET and 48 months for the other group who received CDK4/6 inhibitor in the second line of treatment. However, the difference was not statistically significant (HR=0.91, 95% CI, 0.78–1.09, P-value=0.33). A propensity scores matching analysis showed similar results. Conclusions In this “real-world” population of patients with HR+/HER2− MBC, receiving CDK4/6 inhibitor plus ET as first line of treatment was associated with improved progression free survival compared with patients treated with ET alone in the first-line and CDK4/6 inhibitor plus ET on the second line of treatment.
Citation Format: Gretchen Kimmick, Asal PIlehvari, Wen You, Gloribel Bonilla, Roger Anderson. The impact of treatment sequence of CDK4/6 inhibitor therapy on Metastatic Breast Cancer treatment outcomes in Real-World practice in U.S [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-12.