Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes Journal Article
| Authors: | Chew, S. M.; Ferraro, E.; Safonov, A.; Chen, Y.; Kelly, D.; Razavi, P.; Robson, M.; Seidman, A. D. |
| Article Title: | Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes |
| Abstract: | Background: 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. Materials and methods: 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 Results: 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). Conclusions: 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. © 2024 Elsevier Ltd |
| Keywords: | adult; controlled study; human tissue; cancer surgery; major clinical study; overall survival; cancer recurrence; drug withdrawal; systemic therapy; neuroimaging; nuclear magnetic resonance imaging; follow up; cancer diagnosis; biological marker; progression free survival; cohort analysis; retrospective study; central nervous system; cancer resistance; cancer hormone therapy; brain metastasis; craniotomy; stereotactic radiosurgery; incidental finding; drug substitution; metastatic breast cancer; cyclin dependent kinase 4; hospital anxiety and depression scale; log rank test; cyclin dependent kinase 6; whole brain radiotherapy; clinical outcome; first-line treatment; cancer prognosis; human; male; female; article; palbociclib; prognostic assessment; abemaciclib; ribociclib; graded prognostic assessment; hormone receptor-positive, her2-negative breast cancer; cyclin-dependent kinase 4/6 inhibitor |
| Journal Title: | European Journal of Cancer |
| Volume: | 207 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-08-01 |
| Start Page: | 114175 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2024.114175 |
| PUBMED: | 38896996 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work