The Efficacy and Safety of Dalpiciclib Plus Endocrine Therapy in HR-positive / HER2-negative Advanced Breast Cancer Patients With Visceral Crisis

Inclusion criteria

• Postmenopausal or premenopausal/perimenopausal women aged ≥18 meet one of the following:

A) Previous bilateral oophorectomy, or age ≥60 years; or B) age<60. Natural postmenopausal status (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without other pathological or physiological causes), E2 and FSH at postmenopausal levels; or C) premenopausal/perimenopausal women must receive LHRH agonists therapy during the study.

• Female breast cancer patients diagnosed as HR-positive or HER2-negative by pathological examination are not suitable for surgical resection or radiotherapy for the purpose of cure.

A) ER-positive and/or PR-positive are defined as: ≥ 1% of all tumor cells are positively stained (confirmed by investigator review at the site); B) HER2-negative are defined as: 0/1 + by standard immunohistochemistry (IHC); HER2/CEP17 ratio less than 2.0 by ISH or HER2 gene copy number less than 4 (confirmed by investigator review at the site).

• Any clinical signs or symptoms of symptomatic brain metastasis or visceral metastasis (at least one of the following: carcinomatous meningitis or leptomeningeal metastasis; pleural effusion; ascites; abdominal pain caused by liver or peritoneal metastasis; dyspnea caused by pleural effusion or pulmonary lymphangitis; elevated liver enzymes (> 2 × ULN); rapid elevation of bilirubin > 1.5 × ULN in the absence of Gilbert's syndrome or biliary obstruction; pathologically confirmed bone marrow metastasis; hemoglobin less than 10 g) and patients who cannot tolerate chemotherapy or are considered by the investigator to be inappropriate for chemotherapy or chemotherapy.
• Adequate bone marrow function. Definitions are as follows: a) neutrophil count (ANC) ≥ 1,500/mm3 (1.5 x 109L) (14 without growth factors); b) platelet count (PLT) ≥ 100,000/mm3 (100 x 109L) (7 without correction); c) hemoglobin (Hb) ≥ 8 g/dL (80 g/L) (7 without correction).
• Female subjects who are not postmenopausal or surgically sterile must have a serum pregnancy test within 7 days before the first dose and have a negative result, and are willing to abstain from sexual intercourse or use a medically recognized highly effective contraceptive measure after signing the informed consent, during the study, and for 1 year after administration of the study drug.
• Voluntarily participate in this study, sign informed consent, have good compliance and are willing to cooperate with follow-up.

Exclusion criteria

• Patients contraindicated with dalpiciclib.
• Patients with primary resistance to endocrine therapy. Relapse within 2 years of adjuvant endocrine therapy, or disease progression within 6 months of advanced first-line endocrine therapy.
• Patients with more than 3 lines of prior endocrine therapy.
• Patients previously treated with any CDK4/6 inhibitor.
• Patients with simple bone metastasis.
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 1000 IU/ml), hepatitis C (hepatitis C antibody positive, and HCV-RNA above the lower limit of detection of the analytical method) or combined hepatitis B and C co-infection.
• Within 6 months before enrollment, the following conditions occur: myocardial infarction, severe/unstable angina pectoris, NYHA grade 2 or higher cardiac insufficiency, ≥ grade 2 persistent arrhythmia (according to NCI CTCAE v5.0), atrial fibrillation of any grade, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack) or symptomatic pulmonary embolism.
• Severe infection occurring within 4 weeks (such as intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical practice) before the first dose, or unexplained fever > 38.5℃ during screening/before the first dose.
• Inability to swallow, intestinal obstruction, or other factors affecting drug administration and absorption.
• Known hypersensitivity to dalpiciclib and any of its excipients.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Known history of psychiatric drug abuse or drug use;
• Female patients who are pregnant or lactating.
• Any other condition that the investigator considers the subject unsuitable for this study.