The Dosing Regimen of Pyrotinib in HER2-positive Advanced First-line Breast Cancer: a Phase I Clinical Study

Exclusion Criteria

• •The patient has received any systemic antitumor therapy at the stage of recurrence/metastasis, including any agents targeting EGFR or HER2, systemic chemotherapy, immunotherapy, and more than first-line endocrine therapy, as well as other antitumor therapies deemed by the investigators to be excluded;
• •Tyrosine kinase inhibitor (TKI) preparations or macromolecular antibodies against HER have been used at any stage of breast cancer, except for trastuzumab in the (new) adjuvant stage;
• •In the stage of breast cancer (new) adjuvant therapy, the time interval from the end of systemic therapy (except endocrine therapy) to the discovery of recurrence/metastasis is \<12 months;
• •Patients with active brain metastases with pial metastases confirmed by MRI or lumbar puncture (brain metastases requiring mannitol treatment or with symptoms);
• •Grade≥ 3 peripheral neuropathy according to CTCAE4.0.3 criteria;
• •Patients judged by the investigators to be unsuitable for systematic chemotherapy;
• •Use of endocrine therapy drugs within 7 days prior to randomization;
• •Patients with other malignancies within the previous 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or squamous cell carcinoma (patients with other malignancies occurring more than 5 years after randomization, such as those cured only by surgery, are allowed to be included);
• •Had a major surgical procedure or significant trauma within 4 weeks prior to randomization, or was expected to undergo major surgery;
• •Serious heart disease or discomfort, including but not limited to the following:
• •Previous history of heart failure or systolic dysfunction (LVEF\<50%) High-risk or treatment-requiring angina pectoris or arrhythmias (e.g., second-degree type 2 atrioventricular block or third-degree atrioventricular block, ventricular tachycardia) Clinically significant valvular heart disease ECG showed transmural myocardial infarction Poor hypertension control (systolic blood pressure \>150mmHg and/or diastolic blood pressure \>100mmHg);
• •Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors affecting the administration and absorption of medications;
• •Known allergic history of the drug components of this protocol;
• •A history of immunodeficiency, including HIV infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
• •Presence of third-space fluid accumulation that cannot be controlled by drainage or other methods (e.g., pleural fluid and ascites);
• •Pregnant and lactating female subjects, or fertile subjects who were unwilling to use effective contraception throughout the trial period and within 3 months after the last study dose;
• •Have a serious concomitant disease or other co-medical condition that interferes with planned treatment or any other condition that is not suitable for participation in this study, such as active hepatitis B, a lung infection requiring treatment.