Sergio Cifuentes Canaval, Cancer Research Project Manager at CENEIT Mexico, shared on LinkedIn about recent paper by Sonya M. Chew et al., titled “Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes” published on European Journal of Cancer.
Authors: Sonya M. Chew, Emanuela Ferraro, Anton Safonov, Yuan Chen, Daniel Kelly, Pedram Razavi, Mark Robson, Andrew D. Seidman
“Impact of CDK4/6 Inhibitors on Brain Metastases in HR+/HER2– Metastatic Breast Cancer
Background:
CDK4/6i are widely recommended as first-line treatments in hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer. However, the influence of prior exposure to CDK4/6i on the progression and prognosis of brain metastases (BM) in these patients has not been extensively studied.
This retrospective analysis included:
– CDK-Y cohort (2015-2021): 363 patients with HR+/HER2– BM who received a CDK4/6i.
– 203 received CDK4/6i before BM.
– 133 received CDK4/6i only after BM.
– 27 received CDK4/6i both before and after BM.
– CDK-N cohort (2010-2014): 299 patients with HR+/HER2– BM who did not receive CDK4/6i.
– Outcomes assessed: Central Nervous System Progression-Free Survival (CNS PFS) and Overall Survival (OS) from BM development.
Key Results:
– CNS PFS:
– 21.4 months for those receiving CDK4/6i only after BM.
– 9.4 months for those receiving CDK4/6i both before and after BM (p = 0.006).
– OS:
– 24.9 months for those receiving CDK4/6i only after BM.
– 12.1 months for those receiving CDK4/6i both before and after BM (p = 0.0098).
– OS from BM development:
– 4.3 months for those receiving CDK4/6i before BM.
– 7.7 months for the CDK-N cohort (p = 0.0082).
Conclusions:
The data suggest that prior exposure to CDK4/6i before the development of brain metastases may induce resistance mechanisms that adversely impact CNS PFS and OS when rechallenged with CDK4/6i after BM development. This highlights the necessity of exploring biomarkers to better select patients for CDK4/6i treatment post-BM.
My Clinical Perspective:
I find these results compelling and significant for daily clinical practice. Here are some key takeaways and implications:
1. Patient Selection:
– Careful consideration should be given when selecting patients for CDK4/6i therapy, particularly those with a high risk of developing brain metastases.
– Biomarker development is critical to identify which patients may benefit most from CDK4/6i, especially in the context of BM.
2. Treatment Sequencing:
– The sequencing of CDK4/6i in treatment protocols might need reevaluation. If patients are likely to develop BM, initiating CDK4/6i after BM development may yield better outcomes.
– Alternative therapeutic strategies should be considered for patients who have previously received CDK4/6i before BM development.
3. Personalized Treatment:
– Personalized treatment approaches, including genomic and molecular profiling, could help tailor therapies and improve outcomes for patients with HR+/HER2- metastatic breast cancer.
4. Future Research:
– Further studies are warranted to understand the resistance mechanisms and develop effective biomarkers.
– Clinical trials focusing on combination therapies or alternative agents post-CDK4/6i failure in BM patients are essential.”