Sergio Cifuentes Canaval: Impact of CDK4/6 Inhibitors on Brain Metastases in HR+/HER2- Metastatic Breast Cancer

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.”

Source: Sergio Cifuentes Canaval/LinkedIn