A Study of Pyrotinib Plus Capecitabine in Patients With Brain Metastases From HER2-positive Metastatic Breast Cancer

Inclusion Criteria

• •1. Patient is ≥ 18 years old at the time of signing the informed consent form.
• •2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• •3. HER2-positive: In the pathological examination/rechecking of primary lesions or metastatic lesions performed by the Research site's Pathology Laboratory, at least once the tumor cells defined as 3+ staining by immunohistochemistry, or fluorescence in situ hybridization \[FISH\] confirmed positive
• •4. MRI/enhanced CT confirmed brain metastasis. According to RECIST 1.1, there is at least one measurable brain lesion, and the measurability of extracranial lesions is not required
• •5. Patients Group Cohort A: participants with brain metastases who have not previously been treated with CNS radiotherapy, it should be more than two weeks since the end of the last systemic treatment. Patients with new brain lesions after craniotomy are allowed to be included, provided that they have not received radiotherapy after surgery and are at least 2 weeks away from surgery.
• •Cohort B: Patients with disease progression or new lesions after whole brain radiotherapy (WBRT) or stereotactic radiotherapy (SRT); For lesions that have received local treatment, there is clear evidence of progress in imaging examination, and the lesions that have undergone radiotherapy can be selected as target lesions. If a patient has multiple CNS lesions, only one or a few of which are treated with SRT, and there are lesions that are not treated locally, such patients are still eligible for enrollment in this study.
• •6. Previous treatment
• •Acceptable previous treatments:
• •History of trastuzumab and other anti-HER2 macromolecular antibodies. Any lines of previous chemotherapy. History of endocrine therapy. Patients who have not used capecitabine except for patients with progression at least 6 (for metastatic disease) or 12 (as adjuvant therapy) months after discontinuation of a capecitabine-containing treatment.
• •Concurrent use of bisphosphonates, mannitol and glucocorticoids is allowed, provided that the dosage(⩽2 mg dexamethasone (or equivalent) per day) of glucocorticoids is stable for at least one week before enrollment.
• •7. Expected to survival ≥ 6 months
• •8. Patients must have adequate organ function, criteria as follows.
• •1. Blood routine examination：Absolute Neutrophil Count (ANC)≥1.0×109/L； PLT ≥100×109/L； Hb ≥90g/L
• •2. Blood chemistry test：TBIL ≤1.5 times the upper limit of normal (ULN); ALT and AST≤3 times ULN; For patients with liver metastases, ALT and AST≤5×ULN; BUN and Cr≤1×ULN and creatinine clearance ≥50mL/min (CockcroftGault formula);
• •3. Ultrasonic cardiogram: LVEF≥50%
• •4. 12-lead ECG: The QT interval (QTcF) corrected by Fridericia's method is \< 450 ms/man and \< 470 ms/women.
• •9. Patients need to voluntarily join this study after they fully understand and sign the informed consent form. Patients need to have good compliance and be willing to cooperate with follow-up.