Table 3.

Clinical trials studying the application of CDK4/6 inhibitors in Patients with HER2+ brain metastasis.

Selected inclusion/Exclusion Criteria	Interventions	Primary End point
NCT04334330 ( 62) A Phase II study to Evaluate the Efficacy of Palbociclib, Trastuzumab and Pyrotinib With Fulvestrant in ER/PR+ and HER2+ breast cancer patients with brain metastasis		Status : Recruiting
Estimated Enrollment: 34 - Histologically confirmed ER/PR positive, HER2-positive metastatic breast cancer - Measurable disease in the brain, defined as at least 1 lesion measuring >= 10 mm on MRI at the time of registration - leptomeningeal disease or been treated with WBRT is not allowed	- palbociclib PO daily on days 1-21, combined with trastuzumab IV every three weeks, pyrotinib PO daily and fulvestrant IM every 4 weeks. Cycles repeat every 28 days - No specific drug dosage - Actual Study Start Date : December 4, 2020     Estimated Primary Completion Date : December 30, 2023	Current results: Objective response rate in the CNS: 28.6%, mPFS:10.6 months, The time to progression in the CNS was 8.5 months The median follow-up was 6.3 months duration:3 years
NCT02774681 A Phase II Single Arm Study to evaluate the Efficacy of Palbociclib in Patients With Metastatic HER2-positive Breast Cancer With Brain Metastasis		Status: Terminated Has Results
Estimated Enrollment: 12 - Histologically confirmed HER2-positive metastatic breast cancer - should not have received > 2 lines of chemotherapy for metastatic disease - Measurable disease in the brain, defined as at least 1 lesion measuring >= 5 mm on imaging at the time of registration - Any uncontrolled neurological symptom attributed to CNS metastasis or leptomeningeal disease or Previous treatment with Palbociclib is not allowed	- palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity - trastuzumab IV over 30-90 minutes every 3 weeks - No specific drug dosage - Recruitment period: May 25, 2016- January 28, 2019	No RRR, Stable DiseaseCNS:6, Progressive Disease CNS:6 duration:3 years

RRR, Radiographic Response Rate in the CNS in Patients With HER2-positive Breast Cancer Who Have Brain Metastasis Treated With Palbociclib. No RRR was not calculated as the study did not met statistical analysis criteria due to study closing before total accrual was met.