|
b'18 years old \\u2264 age \\u2264 70 years old, female;' |
|
|
|
|
|
b'BMI 18 ~ 32 kg / m2, including both ends;' |
|
|
|
|
b'Histological or cytologically confirmed recurrent or metastatic breast cancer.' |
|
|
|
|
|
b'According to RECIST v 1.1, patients with measurable and/or unmeasurable lesions:' |
|
|
|
|
|
b'Patients with bone metastases, as long as the bone metastases have never received' |
|
|
|
|
|
b'radiotherapy, and the primary tumor tumours are available for HER2 detection and' |
|
|
|
|
b'Biomarker analysis, which can be enrolled;' |
|
|
|
|
|
b'Patients with local recurrence and unsuitable for radical mastectomy;' |
|
|
|
|
|
b'For bilateral breast cancer, and bilateral HER2 expression is inconsistent, the' |
|
|
|
|
|
b'metastases should be confirmed to be HER2 positive;' |
|
|
|
|
|
b'Anti-HER2 treatment failure for recurrent or metastatic disease;' |
|
|
|
|
|
b'A retrograde or metastatic breast cancer diagnosed as HER2 positive (FISH positive and' |
|
|
|
|
|
b'/ or IHC 3+) by the Department of Pathology diagnosis;' |
|
|
|
|
b'The left ventricular ejection fraction (LVEF) was detected by echocardiography (ECHO)' |
|
|
|
|
|
b'\\u226550% in the baseline period (28 days before the start of the trial);' |
|
|
|
|
|
b'ECOG physical state (PS) is 0-1 points;' |
|
|
|
|
|
b'Expected to survive for more than 3 months;' |
|
|
|
|
|
b'Female patients of childbearing age, patients and/or their partners should agree to' |
|
|
|
|
|
b'use a highly effective non-hormonal contraceptive method or two effective non-hormonal' |
|
|
|
|
|
b'contraceptive methods. Continue to use the appropriate contraceptive measures during' |
|
|
|
|
|
b'the study period and at least 6 months after the last dose;' |
|
|
|
|
|
b'Understand and voluntarily sign the informed consent form.' |
|
|
|
|
|
b'In the screening examination, the blood concentration of patients who have used'
|
|
|
|
|
|
b'pertuzumab in the past is \\u22655\\u03bcg/ml;'
|
|
|
|
|
|
b'In the screening examination, the blood concentration of patients who have used'
|
|
|
|
|
|
b'trastuzumab in the past is \\u22655\\u03bcg/ml;'
|
|
|
|
|
b'Known to be allergic to the study drug or its components;'
|
|
|
|
|
|
b'Subjects with a history of contrast allergies;'
|
|
|
|
|
|
b'There is clinical or radiological evidence of a central nervous system (CNS)'
|
|
|
|
|
|
b'metastasis. For patients with clinically suspected CNS metastases, enhanced CT or'
|
|
|
|
|
|
b'enhanced MRI must be performed within the first 28 days of randomization to exclude'
|
|
|
|
|
|
b'CNS metastasis;'
|
|
|
|
|
|
b'Hematological toxicity caused by previous treatment CTCAE \\u2265 2 persistence (except'
|
|
|
|
|
|
b'hemoglobin) (NCI-CTCAE version 4.03);'
|
|
|
|
|
|
b'There are peripheral neuropathy CTCAE \\u2265 3 (first dose group, peripheral neuropathy'
|
|
|
|
|
|
b'CTCAE \\u2265 2);'
|
|
|
|
|
|
b'A history of other malignancies in the last 5 years, except for cured cervical'
|
|
|
|
|
|
b'carcinoma in situ or basal cell carcinoma or squamous cell carcinoma of the skin;'
|
|
|
|
|
|
b'Uncontrolled high blood pressure (systolic blood pressure greater than 150 mmHg and /'
|
|
|
|
|
|
b'or diastolic blood pressure greater than 100 mmHg), orthostatic hypotension;'
|
|
|
|
|
|
b'Cardiac standard: QTc>480ms. There are factors that can cause QTc prolongation or'
|
|
|
|
|
|
b'arrhythmia such as congestive heart failure, hypokalemia, long QT syndrome (atrial'
|
|
|
|
|
|
b'fibrillation, paroxysmal supraventricular tachycardia). There are any unstable'
|
|
|
|
|
|
b'cardiovascular diseases (including the New York Heart Association NYHA cardiac'
|
|
|
|
|
|
b'function grade III or IV, congestive heart failure, unstable angina, a history of'
|
|
|
|
|
|
b'myocardial infarction within 6 months);'
|
|
|
|
|
|
b'LVEF <50% during the period of neoadjuvant or adjuvant therapy or prior to the end of'
|
|
|
|
|
|
b'treatment with trastuzumab or pertuzumab for injection;'
|
|
|
|
|
|
b'Resting dyspnea caused by complications of advanced malignancies, or other conditions'
|
|
|
|
|
|
b'requiring continuous oxygen therapy;'
|
|
|
|
|
|
b'There are serious, uncontrollable systemic diseases (such as clinically significant'
|
|
|
|
|
|
b'cardiovascular, pulmonary, liver and kidney, digestive or metabolic diseases;'
|
|
|
|
|
|
b'fractures);'
|
|
|
|
|
|
b'Experience major surgery or trauma within 28 days prior to the start of the trial, or'
|
|
|
|
|
|
b'plan for major surgery before the end of the study treatment;'
|
|
|
|
|
|
b'The cumulative dose of anthracycline antibiotics was assessed at baseline (within 28'
|
|
|
|
|
|
b'days prior to the start of the trial) to meet the following criteria:'
|
|
|
|
|
|
b'doxorubicin > 360 mg/m2;'
|
|
|
|
|
|
b'epirubicin > 720 mg/m2;'
|
|
|
|
|
|
b'hydrochloric acid mitoxantrone > 120 mg/m2 and idarubicin (demethoxy'
|
|
|
|
|
|
b'daunorubicin) > 90 mg/m2;'
|
|
|
|
|
|
b'other (such as doxorubicin liposome or other anthracycline antibiotics > 360 mg /'
|
|
|
|
|
|
b'Doxorubicin equivalent dose of m2);'
|
|
|
|
|
|
b'If more than one anthracycline antibiotic is used, the cumulative dose should not'
|
|
|
|
|
|
b'exceed the equivalent dose of doxorubicin of 360 mg/m2;'
|
|
|
|
|
|
b'Have received any trial medication within 28 days prior to the start of the trial;'
|
|
|
|
|
|
b'Have received any therapeutic antibody or vaccine within 28 days prior to the start of'
|
|
|
|
|
|
b'the trial;'
|
|
|
|
|
|
b'Chemotherapy, endocrine therapy, and radiotherapy were administered within 28 days'
|
|
|
|
|
|
b'prior to the start of the trial;'
|
|
|
|
|
|
b'Intravenous infusion of antibiotics to treat infection within 14 days prior to the'
|
|
|
|
|
|
b'tart of the trial;'
|
|
|
|
|
|
b'Daily oral glucocorticoid treatment, equivalent to a dose of >10 mg / day of'
|
|
|
|
|
|
b'methylprednisolone, except for inhaled corticosteroids;'
|
|
|
|
|
|
b'The presence of anti-drug antibodies against trastuzumab or pertuzumab;'
|
|
|
|
|
|
b'Within 7 days prior to the start of the trial, laboratory tests revealed any of the'
|
|
|
|
|
|
b'following abnormalities:'
|
|
|
|
|
|
b'Absolute count of neutral cells <1.5\\xd7109/L;'
|
|
|
|
|
|
b'Platelet count <80.0\\xd7109/L;'
|
|
|
|
|
|
b'Hemoglobin <9 g/dL;'
|
|
|
|
|
|
b'Total Bilirubin > 1.5 \\xd7 normal upper limit (ULN) (unless the patient has'
|
|
|
|
|
|
b"Glibert's syndrome)"
|
|
|
|
|
|
b'AST or ALT > 2.5 \\xd7 ULN'
|
|
|
|
|
|
b'Creatinine clearance (calculated using the Cockcroft_Gault formula) < 50 mL / min'
|
|
|
|
|
|
b'International normalized ratio (INR) and Activated partial thromboplastin time or'
|
|
|
|
|
|
b'partial thromboplastin time (APPT or PT) > 1.5 x ULN (unless treated for'
|
|
|
|
|
|
b'coagulation abnormalities);'
|
|
|
|
|
|
b'Hepatitis B surface antigen positive and HBV-DNA test \\u2265 lower limit of detection;'
|
|
|
|
|
|
b'hepatitis C antibody positive; HIV antibody positive;'
|
|
|
|
|
|
b'Pregnant or lactating women;'
|
|
|
|
|
|
b'Other circumstances judged by the investigator are not suitable for participation in'
|
|
|
|
|
|
b'the study.'
|
|
|
|