Efficacy of everolimus plus endocrine therapy after CDK4/6 inhibitors in patients with HR-positive, HER2-negative metastatic breast cancer

A multicenter retrospective cohort study in France evaluated the efficacy of everolimus plus endocrine therapy in patients with HR-positive, HER2-negative metastatic breast cancer (HR+ HER2- mBC) who were or were not previously treated with CDK4/6 inhibitors. The study included 325 patients treated with everolimus between 2012 and 2022. Among these patients, 75 (23%) had been pretreated with CDK4/6 inhibitors. In the overall population, median progression-free survival was 6.4 months (95% CI 5.5-7.1) and the median overall survival was 25 months (21.8-28.1). Median PFS was 5.3 months (95% CI 4.6-7.1) among those who were previously exposed to CDK4/6 inhibitors and 6.7 months (5.8-7.6) among those who had not been treated with CDK4/6 inhibitors (p=0.046), with median OS 21.8 months (18.5-25.5) and 27.3 months (23.2-30.2), respectively (p=0.01). Factors associated with improved PFS were lack of liver metastases (p<0.001), no prior exposure to metastatic chemotherapy (p=0.001), a lower tumor grade (p=0.005, no prior treatment with CDK4/6 inhibitors (p=0.006), and a better performance status (p=0.008). The authors conclude that HR+ HER2- mBC patients who had prior exposure to CDK4/6 inhibitors experienced a shorter median PFS benefit from everolimus-based therapy compared to those who were CDK4/6 inhibitor-naïve.