Everolimus plus exemestane in patients with hormone receptor-positive advanced breast cancer previously treated with or without CDK 4/6 inhibitor

Purpose Cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with endocrine therapy, are widely used as first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer (HR + ABC) and optimal treatment after failure to CDK 4/6 inhibitors is an important clinical question, but there is limited data on everolimus plus exemestane after CDK 4/6 inhibitors. Method We included 202 HR + ABC patients who received everolimus plus exemestane between 2014 and 2020. Clinical outcomes, including progression-free survival (PFS) and response, according to previous CDK 4/6 inhibitors were analyzed. Results The patients who received CDK 4/6 inhibitors before everolimus plus exemestane showed significantly shorter PFS than those who didn’t receive prior CDK 4/6 inhibitors (2.99 vs. 8.58, 95% CI: 0.42–5.57 vs . 6.57–10.59, p  < 0.001). Similarly, among 109 patients who received only one line of endocrine treatment (ET) before everolimus plus exemestane, patients with prior CDK 4/6 inhibitors showed significantly shorter PFS compared to those with ET only (2.76 vs . 8.58, 95% CI: 2.11–3.41 vs . 8.58–13.1, p  < 0.001). Response rate was also lower in patients who treated with previous CDK 4/6 inhibitors than those who didn’t (0.0% vs 20.2%, p  = 0.064). Conclusion CDK 4/6 inhibitors are a major breakthrough for patients with HR + ABC, but the subsequent treatment after failure is a clinical challenge. Everolimus plus exemestane is a viable clinical option in the setting, but with poorer clinical outcomes in patients previously treated with CDK 4/6 inhibitors. More research on the optimal therapeutic strategies in the setting is warranted.