Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes

• Published in: European journal of cancer (1990) 2024-08, Vol.207, p.114175, Article 114175
• Main Authors: Chew, Sonya M., Ferraro, Emanuela, Safonov, Anton, Chen, Yuan, Kelly, Daniel, Razavi, Pedram, Robson, Mark, Seidman, Andrew D.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Brain metastasis; Brain Neoplasms - drug therapy; Brain Neoplasms - secondary; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Central nervous system; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-dependent kinase 4/6 inhibitor; Cyclin-Dependent Kinase 6 - antagonists & inhibitors; Female; Humans; Metastatic breast cancer; Middle Aged; Overall survival; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.114175

Cyclin dependent kinase 4/6 inhibitors (CDK4/6i) are recommended 1st line treatments in HR+HER2- metastatic breast cancer. However, the impact of prior CDK4/6i on the natural history of brain metastases (BM) is not well described. We reviewed retrospective data for 363 patients with HR+HER2- BM who received a CDK4/6i (CDK-Y) between 1 Jan 2015 to 31 July 2021 and 299 patients with HR+HER2- BM who did not receive a CDK4/6i (CDK-N) between 1 Jan 2010 to 31 Dec 2014. CNS PFS and OS were assessed in patients who received CDK4/6i after BM. OS from the time of BM development was assessed between patients who received CDK4/6i before BM and the CDK-N cohort In the CDK-Y cohort of 363 patients, 203 (56 %) received a CDK4/6i before BM, 133 (37 %) received a CDK4/6i only after BM and 27 (7 %) received a CDK4/6i both before and after BM. Median CNS PFS was 21.4 months for patients receiving a CDK4/6i only after BM and 9.4 months for patients who received CDK4/6i both before and after BM (p = 0.006). Median OS was 24.9 months for patients receiving a CDK4/6i only after BM and 12.1 months for patients who received CDK4/6i both before and after BM (p = 0.0098). Median OS from time of BM development for patients receiving a CDK4/6i before BM versus the CDK-N cohort was 4.3 months and 7.7 months respectively (p = 0.0082). CDK4/6i exposure prior to BM may lead to development of resistance mechanisms which in turn reduces CNS PFS and OS upon rechallenging with a CDK4/6i after BM development. This motivates investigation of biomarkers for patient selection. •Real world data of impact of CDK4/6i on breast cancer brain metastases outcomes.•Improved median overall survival if CDK4/6i received only after brain metastases.•Potential development of resistance mechanisms with CDK4/6i exposure.•Rechallenging with CDK4/6i after brain metastases results in reduced efficacy.