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.
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.
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.
摘要：
背景：细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）是HR+HER2转移性乳腺癌的一线治疗方法。然而,之前的CDK4/6i对脑转移(BM)自然史的影响没有得到很好的描述.
方法：我们回顾了2015年1月1日至2021年7月31日期间接受CDK4/6i（CDK-Y）的363例HR+HER2-BM患者和2010年1月1日至2014年12月31日期间未接受CDK4/6i（CDK-N）的299例HR+HER2-BM患者的回顾性数据。在BM后接受CDK4/6i的患者中评估CNSPFS和OS。在BM之前接受CDK4/6i的患者和CDK-N队列之间评估了BM发展时间的OS结果：在363例患者的CDK-Y队列中，203（56%）在BM之前接受了CDK4/6i，133（37％）仅在BM后接受CDK4/6i，而27（7％）在BM前后均接受CDK4/6i。仅在BM后接受CDK4/6i的患者的CNSPFS中位数为21.4个月，在BM前后接受CDK4/6i的患者为9.4个月（p=0.006）。仅在BM后接受CDK4/6i的患者的中位OS为24.9个月，在BM前后接受CDK4/6i的患者的中位OS为12.1个月（p=0.0098）。在BM之前接受CDK4/6i的患者与CDK-N队列相比，从BM发展时间的中位OS分别为4.3个月和7.7个月（p=0.0082）。
结论：在BM之前暴露CDK4/6i可能导致耐药机制的发展，进而在BM发展后用CDK4/6i重新攻击时降低CNSPFS和OS。这激发了用于患者选择的生物标志物的研究。
方法：我们回顾了2015年1月1日至2021年7月31日期间接受CDK4/6i（CDK-Y）的363例HR+HER2-BM患者和2010年1月1日至2014年12月31日期间未接受CDK4/6i（CDK-N）的299例HR+HER2-BM患者的回顾性数据。在BM后接受CDK4/6i的患者中评估CNSPFS和OS。在BM之前接受CDK4/6i的患者和CDK-N队列之间评估了BM发展时间的OS结果：在363例患者的CDK-Y队列中，203（56%）在BM之前接受了CDK4/6i，133（37％）仅在BM后接受CDK4/6i，而27（7％）在BM前后均接受CDK4/6i。仅在BM后接受CDK4/6i的患者的CNSPFS中位数为21.4个月，在BM前后接受CDK4/6i的患者为9.4个月（p=0.006）。仅在BM后接受CDK4/6i的患者的中位OS为24.9个月，在BM前后接受CDK4/6i的患者的中位OS为12.1个月（p=0.0098）。在BM之前接受CDK4/6i的患者与CDK-N队列相比，从BM发展时间的中位OS分别为4.3个月和7.7个月（p=0.0082）。
结论：在BM之前暴露CDK4/6i可能导致耐药机制的发展，进而在BM发展后用CDK4/6i重新攻击时降低CNSPFS和OS。这激发了用于患者选择的生物标志物的研究。
