Cyclin-dependent kinase 4/6 inhibitors combined with stereotactic ablative radiotherapy in oligometastatic HR-positive/HER2-negative breast cancer patients

Abstract Objectives Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have significantly improved the survival of patients with hormone receptor-positive HER2-negative advanced breast cancer (ABC). Although stereotactic ablative radiotherapy (SABR) is used more often in routine clinical practice, data on the safety and efficacy of combining SABR with CDK4/6i are lacking. Herein, we present the results of SABR combined with CDK4/6i in ABC. Methods Patients with ABC who received CDK4/6i and SABR between 2018 and 2023 were analysed. Results Among 384 patients treated with CDK4/6i, 34 patients received 44 courses of SABR. Two-year progression-free survival (PFS) was 63.6% (95% CI, 45.8-88.3), and the median PFS was 32 months. Three-year overall survival (OS) was 88.9% (95% CI, 77.7-100). Two-year local control (LC) was 92.7% (95% CI, 83.4-100). Median OS and LC were not reached. The subgroup analysis showed the difference in survival between oligometastatic patients (OMD) and non-OMD subgroup. Two-year PFS was 69.2% (95% CI, 44.5-100) in OMD compared with 57.4% (95% CI, 36-91.7) in the non-OMD (P = .042). Three-year OS was 90% (95% CI, 73.2-100) in OMD compared with 86.2% (95% CI, 70-100) in the non-OMD (P = .67). Median PFS and OS in the non-OMD were 26 and 56 months, respectively, and were not reached in OMD. Fifteen patients required CDK4/6i dose reduction, and 2 discontinued treatment due to toxicity. No difference in high-grade toxicity was observed between the sequential and concurrent SABR. Conclusion The addition of SABR to CDK4/6i seems to be safe and effective, especially in patients with oligometastatic disease. Advances in knowledge In advanced breast cancer patients treated with CDK4/6i, SABR provides a high local control and may provide additional benefit in an oligometastatic setting.