Clinical outcomes with statins and CDK4/6 inhibitors in patients with metastatic HR+/HER2- breast cancer.

e13093 Background: With the increasing use of cyclin-dependent kinase inhibitors (CDK4/6i) combined with endocrine therapy (ET) as the standard first-line treatment of hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC), there is a need to optimize therapeutic efficacy to delay chemotherapy. Statins, or HMG-CoA Reductase inhibitors, have generated attention for their anti-cancer properties and role in augmenting anti-neoplastic therapies. In early-stage HR+/HER2-breast cancer, the addition of statins to adjuvant ET has shown reduced recurrence and mortality. We evaluated the association between statin use and clinical outcomes of HR+/HER2- MBC patients on CDK4/6i therapy. Methods: This retrospective study examined patients with HR+/HER2- MBC who received treatment with CDK 4/6i and ET between 6/2019 and 4/2022 at Winship Cancer Institute of Emory University. Patient outcomes, statin use, age, race, line of therapy, ET partner, and de novo MBC status were collected up to 10/2024. Primary outcomes were progression free survival (PFS) and overall survival (OS). PFS was defined as time from CDK4/6i start date to date of progression, death, last follow up or date of CDK4/6i stop, whichever occurred first. Overall Survival (OS) was the time from CDK4/6i start date to date of death or last follow up for surviving patients. Multivariate cox proportional hazards models were applied for time-to-event analyses, adjusting for covariates such as age, race, and de novo MBC status. Results: A total of 342 patients were identified. Of those, 62 (18.3%) were on a statin at baseline (statin-bl) and 35 (10.23%) started a statin after initiation of CDK4/6i therapy; for our analysis, the latter group was excluded. Median age for statin-bl was 66 vs 56 years for the no statin group. Median PFS in months for patients on statin-bl and no statin was 34 (95% CI 18, 49.2) and 24.1 (95% CI 22.1, 28.2) respectively with a hazard ratio (HR) of 0.79 (p = 0.204). Median OS in months for patients on statin-bl and no statin was 57.2 (95% CI 43.3, NA) and 65.9 (95% CI 58.2, 74.5) respectively with a HR of 0.91 (p = 0.69). In a subgroup analysis of patients on first line CDK4/6i and ET (n = 263), HR for PFS was 0.73 (p = 0.14) and OS was 0.76 (p = 0.32). Conclusions: Although statin use during CDK4/6i therapy did not demonstrate a statistically significant association with PFS or OS, we observed a 10-month increase in median PFS for patients in the statin-bl group. Multivariate analysis suggested a trend towards improvement in PFS and OS for the statin-bl group and this trend was more pronounced in patients receiving first line CDK4/6i. Our study was limited by the absence of comorbidity data, which may have impacted survival outcomes. Further investigations with a larger cohort and comprehensive comorbidity data are needed to better understand the impact of statin use during CDK4/6i and ET on breast cancer outcomes.