Overall survival after CDK4/6 inhibitor dose reduction in women with metastatic breast cancer

BackgroundBreast cancer is the most common cancer in women, and the first-line treatment for patients with hormone-receptor positive/HER2-negative metastatic breast cancer is CDK4/6 inhibitor plus endocrine therapy. Understanding the impact of CDK4/6 inhibitor dose reduction, which occurs in about half of the patients, is important.MethodsThis real-world cohort study is based on electronic health records from Capital Region of Denmark. All women with metastatic breast cancer initiating first-line treatment with CDK4/6 inhibitor between May 2017 and October 2022 were included.ResultsA total of 546 patients were eligible for inclusion in the 12-week landmark analysis and 192 (35%) experienced dose reduction. These patients were older, had worse ECOG PS, more received prior adjuvant endocrine treatment, and more received fulvestrant as the endocrine backbone. Dose reduction was associated with reduced overall survival (39.9 vs. 54.3 months) and shorter treatment duration (18.0 vs. 26.9 months). Adjusted hazard ratio for death was 1.38 (95% CI: 1.01–1.89).ConclusionsDose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with significantly higher mortality and shorter treatment duration. These findings contrast with previous analyses showing no effect of dose reduction, likely due to considering immortal time bias in this study.