Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer

TL;DR

Switching CDK4/6 inhibitors plus endocrine therapy improves treatment duration in metastatic breast cancer patients compared to switching to endocrine therapy alone.

Contribution

This study demonstrates that switching CDK4/6i + ET is more effective than switching to ET monotherapy in a large real-world cohort.

Findings

Switching from CDK4/6i + ET to another CDK4/6i + ET significantly prolonged time to discontinuation compared to switching to ET monotherapy.

The order of palbociclib and abemaciclib administration did not significantly affect treatment duration in patients switching CDK4/6i + ET.

Switching CDK4/6i + ET is a viable option regardless of PIK3CA mutation status.

Abstract

Recent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i + ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who received CDK4/6i + ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i + ET to another CDK4/6i + ET, the second-line TTD and total TTD of first- and second-line therapies (n = 542) were significantly longer than those in patients who switched from CDK4/6i + ET to ET monotherapy (n = 490) (the second-line TTD: 11.2 vs. 4.9 months, p < 0.01; total TTD: 25.1 vs. 20.5 months, p < 0.01). The order of palbociclib and abemaciclib administration did not significantly affect the second-line or total TTD in patients who switched from one CDK4/6i + ET to another CDK4/6i + ET. Switching from one CDK4/6i + ET to another CDK4/6i + ET resulted in a significantly longer TTD than switching to ET monotherapy. Considering the phase III clinical trial results of capivasertib, switching to CDK4/6i + ET is a viable therapeutic option regardless of the PIK3CA mutation status.

The online version contains supplementary material available at 10.1007/s12282-025-01768-6.

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