Approximately 5-15% breast cancer patients develop brain metastases. Current local treatments (surgery/radiotherapy) are associated with significant complications, and systemic treatments have limited efficacy. Although new-generation ADC drugs, such as trastuzumab deruxtecan, have demonstrated breakthrough efficacy in patients with brain metastases, the mechanisms of action are not fully elucidated, moreover the current treatment regimens still have limitations for patients with HER2-low expressing, safer and more effective systemic treatment options are urgently needed to improve patient survival. BCBM-006 is an open-label, prospective, single-arm, single-center Phase II clinical study to evaluate the relationship between cerebrospinal fluid drug concentration and efficacy of trastuzumab deruxtecan in central nervous system metastatic breast cancer, and explore the incidence of leptomeningeal metastases diagnosed via lumbar puncture in patients with brain parenchymal metastases, facilitate early intervention to improve prognosis.
1. ≥18 years（2007-06）, any gender. 2. ECOG Performance Status 0-2. 3. Evidence of local recurrence or metastatic breast cancer not amenable to curative surgery or radiotherapy, and planned for intravenous trastuzumab deruxtecan treatment.
ANC≥1.5×109/L;
PLT≥75×109/L;
Hb≥90 g/L (allowing blood transfusion or medication to ensure hemoglobin content);
1. Presence of uncontrolled third-space fluid accumulation (e.g., large pleural effusion or ascites) not manageable by drainage or other methods, deemed unsuitable for enrollment by the investigator.
Severe cardiac rhythm or conduction abnormalities requiring clinical intervention, such as ventricular arrhythmia, II-III degree atrioventricular block, etc.
Cardiac insufficiency of Class III~IV according to the New York Heart Association (NYHA) criteria.
Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular/cerebrovascular events within 6 months prior to the first dose.
The study population consisted of patients with recurrent metastatic breast cancer, divided into a control cohort without central nervous system metastases (N=10) and an experimental cohort with central nervous system metastases (N=30-50). Ptients in China
Cohort
Prospective
No Interventions
Other interventionno interventions
Correlation between cerebrospinal fluid trastuzumab deruxtecan concentration and intracranial objective response
Spearman correlation coefficient between cerebrospinal fluid trastuzumab deruxtecan concentration (ng/mL), measured by iquid chromatography-tandem mass spectrometry (LC-MS/MS), and intracranial objective response assessed according to RANO-BM criteria.
Objective Response Rate (ORR)
Percentage of participants achieving complete response (CR) or partial response (PR) according to RECIST version 1.1.
Intracranial Objective Response Rate (CNS-ORR)
Percentage of participants achieving complete response (CR) or partial response (PR) in intracranial lesions according to RANO-BM criteria.
Clinical Benefit Rate (CBR)
Percentage of participants achieving complete response (CR), partial response (PR), or stable disease (SD) lasting at least 24 weeks according to RECIST version 1.1.
Intracranial Clinical Benefit Rate (CNS-CBR)
Percentage of participants achieving complete response (CR), partial response (PR), or stable disease (SD) lasting at least 24 weeks in intracranial lesions according to RANO-BM criteria.
Frequency of genomic alterations associated with intracranial efficacy
Frequency of genomic alterations, including ESR1 and other driver gene alterations, detected by next-generation sequencing (NGS) in tumor tissue, cerebrospinal fluid, and circulating tumor cells (CTCs), and their association with intracranial efficacy.
Correlation between HER2 expression level and cerebrospinal fluid trastuzumab deruxtecan concentration
Spearman correlation coefficient between HER2 expression level assessed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) in tumor tissue and cerebrospinal fluid trastuzumab deruxtecan concentration (ng/mL) measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
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