| Eligibility |
Inclusion Criteria:
1. Subjects voluntarily joined the study, signed informed consent, and had good
compliance.
2. Postmenopausal or premenopausal perimenopausal female patients aged = 18 years, Meet
one of the following:
Previous bilateral oophorectomy, or age = 60 years; or Age <60, natural postmenopausal
state (defined as regular months for at least 12 consecutive months After spontaneous
cessation and no other pathological or physiological reasons), E2 and follicle
stimulating hormone (FSH) in menopause Post-level; or Pre-menopausal or perimenopausal
female patients can also be included, but must be willing to receive treatment with
luteinizing hormone releasing hormone (LHRH) agonists;
3. Patients with HR+/HER2+ recurrent or metastatic breast cancer confirmed by
histopathology; HER2 positivity is defined by standard of 3+ staining by
immunohistochemical staining (IHC) or positive for in situ hybridization (ISH);
Estrogen receptor (ER) or Progesterone receptor (PR) positive is defined as the
percentage of cells positive for ER or PR expression = 10%; Local recurrence needs to
be confirmed by the physician that is unresectable
4. At least one extracranial measurable lesion according to Response Evaluation Criteria
in Solid Tumors (RECIST) criteria version 1.1.
5. No systemic treatment in metastatic setting. At least 12-month interval between the
time of last dose of trastuzumab in adjuvant treatment and the date of diagnosis with
recurrent or metastatic breast cancer
6. Had received endocrine therapy in adjuvant setting.
7. Eastern Cooperative Oncology Group Performance Status of 0-1.
8. Life expectancy = 12 weeks.
9. Adequate function of major organs meets the following requirements (no blood
components and cell growth factors have been used within 14 days before
randomization):
Neutrophils = 1.5×10^9/L, Platelets = 100×10^9/L, Hemoglobin = 90g/L, Total bilirubin= 1.5
× the upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) = 2.5 × ULN, blood urea nitrogen(BUN) and Cr = 1.5 × ULN, Left
ventricular ejection fraction (LVEF) = 50%, QTcF(Fridericia correction) = 470 ms,
International normalized ratio(INR)=1.5 × ULN, activated partial thromboplastin time(APTT)
= 1.5 × ULN
Exclusion Criteria:
1. Meningeal metastasis or active brain parenchymal metastasis. Patients with clinically
stable brain parenchymal metastases can be included, including asymptomatic brain
metastases that have not received local treatment; or patients who have previously
received central nervous system metastasis therapy (radiotherapy or surgery), if
imaging confirms that stability has been maintained for at least 4 weeks, and have
stopped symptomatic treatment (including hormones and mannitol, etc.) for more than 2
weeks
2. Visceral crisis.
3. Previously received any CDK4/6 inhibitor treatment.
4. Inability to swallow, intestinal obstruction or other factors affecting the
administration and absorption of the drug.
5. Patients with other malignant tumors within 5 years or at the same time( except for
cured skin basal cell carcinoma and cervical carcinoma in situ).
6. Have undergone major surgical procedures or significant trauma within 4 weeks prior to
randomization, or are expected to undergo major surgery.
7. Pregnant women, lactating female, or women of childbearing age who are unwilling to
take effective contraceptive measures.
8. Have a history of allergies to the drug components of this regimen.
9. Patients with active HBV and HCV infection; stable hepatitis B after drug treatment
(HBV virus copy number is higher than the upper limit of reference value) and cured
hepatitis C patients (HCV virus copy number exceeds the lower limit of detection
method).
10. History of immunodeficiency, including HIV positive, or other acquired or congenital
immunodeficiency disease, history of organ transplantation.
11. History of cardiac dysfunction, include (1)angina (2)clinical significant arrythmia or
require drug intervention (3)myocardial infarction (4)heart failure (5) other cardiac
dysfunction (judged by the physician); any cardiac or nephric abnormal = grade 2 found
in screening.
12. Female patients who are pregnancy, lactation or women who are of childbearing
potential tested positive in baseline pregnancy test.
13. Childbearing female who refuses to accept any contraception practice.
14. Determined by the physician, any serious coexisting disease might be harmful to the
patient's safety or avoid the patients from accomplishing the treatment(e.g serious
hypertension, diabetes, thyroid dysfunction,active infection etc.).
15. History of neurological or psychiatric disorders, including epilepsy or dementia.
16. Severe infections within 4 weeks prior to first dose (eg, intravenous infusion of
antibiotics, antifungal or antiviral drugs according to clinical protocols), or
unexplained fever (T > 38.3 °C ) during screening or prior to first administration.
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