Inclusion Criteria:
1. Patients must be ≥18 years old;
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
3. Pathologically confirmed HER2-positive invasive breast cancer with metastatic
disease; patients with no pathological or cytologically confirmed metastatic disease
should obtain clear evidence of metastasis through physical examination or
radiological examination; Note: Positive HER2 -positive refers in the pathological
examination/rechecking of primary lesions or metastatic lesions performed by the
Research site's Pathology Laboratory, at least once the tumour cells defined as 3+
staining by immunohistochemistry, or fluorescence in situ hybridization (FISH)
confirmed positive;
4. Fam-trastuzumab deruxtecan-nxki or A1811 had failed treatment for active brain
metastasis and had received no local radiotherapy previously. Patients with new
lesions in the brain after craniotomy are allowed to be included, provided that
radiotherapy is not performed after surgery;
5. Enhanced MRI confirmed brain metastasis. According to RANO criteria, there is at
least one measurable brain lesion, and the measurability of extracranial lesions is
not required;
6. Previous treatment:Capecitabine is not allowed, except for patients without
progression or intolerance during use and no relapse at least 6 months (as
neoadjuvant /adjuvant therapy) after discontinuation of a capecitabine-containing
treatment. Pyrotinib is not allowed, except for patients without progression or
intolerance during use and no relapse at least 6 months (as neoadjuvant /adjuvant
therapy) after discontinuation of a pyrotinib-containing treatment ; Patients who
have not previously used pyrotinib , but have used pyrotinib in the neoadjuvant /
adjuvant phase, have not proven disease progression or intolerance during use, and
have relapsed 6 months after the last dose are allowed to be enrolled; Concurrent
use of bisphosphonates, mannitol and glucocorticoids is allowed, provided that the
dosage (<2 mg dexamethasone [or equivalent])
7. Expected survival period of 3 months;
8. Patients must have adequate organ function, criteria as follows: Blood routine test
(no blood transfusion within 14 days, no correction of Granulocyte
colony-stimulating factor(G-CSF) and other hematopoietic stimulating factors):
Absolute Neutrophil Count (ANC) 1.5X10^9 / L; PLT 75X10^9 / L; Hemoglobin（Hb） 90g /
L; Blood chemistry test:total bilirubin (TBIL) ≤1.5 times the upper limit of normal
(ULN); Alanine transaminase(ALT) and Aspartate transaminase(AST) ≤3 times ULN; For
patients with liver metastases, ALT and AST ≤5 times ULN(Upper Limit of Normal);
Blood urea nitrogen(BUN) and creatinine(Cr) ≤1 times ULN and creatinine clearance ≥
50 mL/min (CockcroftGault formula);Ultrasonic cardiogram: left ventricular ejection
fraction (LVEF) ≥50%; Electrocardiograph (ECG): The QT interval corrected by
Fridericia's formula (QTcF)is less than 450 ms for males and less than 470 ms for
females.
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.
Exclusion Criteria:
1. Previous treatment for active brain metastases included other anti-tumor therapy
except for T-DXd or A1811;
2. Active brain metastases requiring radiotherapy; Patients with leptomeningeal
metastasis (diagnosed by imaging/positive cerebrospinal fluid cytology) or a clear
indication of clinically significant leptomeningeal involvement;
3. Central Nervous System(CNS) complications that require urgent neurosurgical
intervention (e.g. resection, shunt placement). Patients with poorly response brain
metastases after dehydration treatment and glucocorticoid treatment, such as
uncontrollable increase in intracranial pressure, jet vomiting, mental disorders,
epilepsy, cognitive impairment, etc;
4. Third space fluid that cannot be controlled by drainage or other methods (such as
large amounts of pleural fluid and ascites);
5. Patients who have received anti-tumor radiotherapy or surgery within 2 weeks before
enrollment (minor surgery, such as tumor biopsy, thoracentesis,intravenous
catheterization or the like are allowed); patients who have received endocrine
therapy within 1 week before enrollment; patients who have received anti-tumor
chemotherapy, molecular targeted therapy or immunotherapy before enrollment within 2
weeks or 5 half-lives from the first study dose (shorter);
6. Participated in clinical trials of other new drugs within 4 weeks before enrollment;
7. Concurrently treated, or who has been treated with HER2 tyrosine kinase
inhibitors(including lapatinib, neratinib, pyrotinib, etc.);
8. History of other malignant tumours within 3 years, excluding cured cervical
carcinoma in situ, skin basal cell carcinoma , skin squamous cell carcinoma or
papillary thyroid carcinoma;
9. There are serious and/or uncontrolled complications that may affect participation,
including any of the following:1) Dysphagia, chronic diarrhoea and intestinal
obstruction and factors that affect the administration and absorption of the drug;2)
Allergic constitution; allergic to the study drug; history of immunodeficiency,
including HIV positive, or other acquired or congenital immunodeficiency diseases;
history of organ transplantation;3) History of severe heart disease, including:
myocardial infarction and heart failure; any other heart disease that is not
suitable for participation (investigator assessment);4) Infection;
10. Female patients during pregnancy and lactation; fertile female patients who tested
positive on a baseline pregnancy test; female patients of childbearing age who are
unwilling to take effective contraceptive measures during the trial.
11. Any other circumstances that are not suitable for inclusion in this study
(investigator assessment)
