combination followed by maintenance chemotherapy versus cdk4/6 inhibitor combined with endocrine therapy for hr low/her2-negative advanced breast cancer: a prospective, randomized, open-label phase ⅱ clinical trial

Conditions: Advanced Breast Cancer; Treatment; HR Low/HER2 Negative

Summary: to observe the differences in the efficacy of combination followed by maintenance chemotherapy versus cdk4/6 inhibitor combined with endocrine therapy in hr low expression /her2 negative advanced breast cancer, and to provide new evidence for the best treatment of hr low expression /her2 negative advanced breast cancer, and to explore the efficacy and safety of combined/maintenance chemotherapy.

to observe the differences in the efficacy of combination followed by maintenance chemotherapy versus cdk4/6 inhibitor combined with endocrine therapy in hr low expression /her2 negative advanced breast cancer, and to provide new evidence for the best treatment of hr low expression /her2 negative advanced breast cancer, and to explore the efficacy and safety of combined/maintenance chemotherapy.

Eligibility criteria:
inclusion criteria: 1. age ≥18 years old; invasive breast cancer with metastatic disease confirmed by histological or cytological examination; patients without pathologically or cytologically confirmed metastatic disease should have clear evidence of metastasis by physical examination or radiological studies; 2. the most recent pathological report of biopsy confirmed hr low expression and her2 negative. 1. hr low expression was defined as 1-50% er expression by immunohistochemistry (ihc); or er\<1% and pr≥1%; patients with er expression of 1-10% or er-/ pr-positive patients were eligible for inclusion after careful evaluation by the investigator, and those with a small tumor burden and candidates for endocrine therapy were eligible. 2. her2-negative definition: ihc 0 or 1+; if the ihc was 2+, it was confirmed negative by fluorescence in situ hybridization (fish). 3. at least one measurable lesion; 4. no previous salvage chemotherapy for metastatic disease was required, and first-line endocrine therapy was allowed; 5. no previous cdk4/6 inhibitor; for adjuvant cdk4/6i treatment, recurrence and metastasis were required more than 1 year after drug withdrawal. 6. eastern cooperative oncology group performance status (ecog ps) 0-1, life expectancy is more than 12 weeks; 7. adequate function of major organs. 8. all adverse events recovered to grade 1 or less before enrollment (nci ctcae version 5.0); 9. patients without major organ dysfunction and heart disease; 10. women and men of childbearing potential must agree to use appropriate contraception before and during study participation. exclusion criteria: 1. symptomatic, uncontrolled brain or leptomeningeal metastases; patients who had received previous systemic radical treatment for brain metastases (radiotherapy or surgery), if stable disease had been maintained for at least 1 month as confirmed by imaging, and if systemic hormone therapy (dose 10mg/ day prednisone or other effective hormones) for more than 2 weeks without clinical symptoms. 2. patients received radiotherapy, chemotherapy, major surgery, targeted therapy or immunotherapy within 2 weeks before enrollment; patients received endocrine therapy within 1 week before enrollment. chemotherapy with nitrosourea or mitomycin was administered within 6 weeks before enrollment. 3. participated in other clinical trials of new drugs within 4 weeks before enrollment; 4. there can not be controlled by drainage or pneumatic methods third space effusion; 5. patients with other malignant tumors within the past 3 years, excluding radical cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma; 6. suffering from serious or uncontrolled diseases, including but not limited to: 1) active viral infection, such as hiv or hbv active (hbsag positive and hbv-dna≥103, hepatitis c antibody positive); 2) history of severe cardiovascular disease: uncontrolled hypertension; myocardial infarction, unstable arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. patients with nyha class ⅲ-ⅳ cardiac dysfunction, or left ventricular ejection fraction (lvef) 50% by echocardiography; 3) severe infection (e.g., intravenous antibiotic, antifungal, or antiviral therapy according to clinical practice) within 4 weeks prior to the first dose or unexplained fever during screening/before the first dose; 38.3°c (fever due to cancer, as judged by the investigator, was eligible); 7. patients with a history of psychotropic drug abuse and unable to abstain or with mental disorders; or accompanied by swallowing and absorption dysfunction; 8. patients with other concomitant diseases that seriously endanger the safety of patients or affect the completion of the study according to the judgment of the investigators; 9. patients with known history of allergy to the components of this regimen; a history of immunodeficiency, including testing positive for hiv, hcv or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation; 10. pregnant or lactating women; 11. patients deemed unsuitable for inclusion by the investigators.