| 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 and =
75 years old,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 FSH in menopause Post-level; or
- Pre-menopausal or perimenopausal female patients can also be included, but must
be willing to receive treatment with 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 = 1%
- 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. Prior treatment:
- Previously received no more than 1 prior lines of systemic treatment with
trastuzumab regimen for repetitive metastatic diabetes [including anti-HER2 ADC,
subsequent meaning is the same]
1. The early stage includes trastuzumab-containing regimen treatment, or
trastuzumab-containing regimen that relapses more than 1 year after the end
of adjuvant treatment, and subsequent treatment is included as the
first-line anti-HER2 treatment;
2. The first-line treatment fails with the trastuzumab-containing regimen, or
the trastuzumab-containing regimen recurs during the adjuvant treatment or
relapses within 1 year after the adjuvant treatment ends, the follow-up
treatment will be included as the second-line anti-HER2 treatment;
- Have not received anti-HER2 TKI treatment before or received but did not prove
that the treatment failed;
- Past endocrine therapy has not proven resistance to aromatase inhibitors
(definition of resistance: recurrence during or within 1 year after treatment
with adjuvant aromatase inhibitors, received aromatase inhibitors in the
recurrence and metastasis stage and disease progression), follow-up Letrozole is
selected for endocrine therapy. Past endocrine therapy has aromatase inhibitor
resistance, and follow-up endocrine therapy is fulvestrant.
6. Eastern Cooperative Oncology Group Performance Status of 0-1.
7. Life expectancy = 12 weeks.
8. 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 = 90×10^9/L
- Hemoglobin = 90g/L
- Total bilirubin= 1.5 × the upper limit of normal (ULN)
- ALT and AST = 2.5 × ULN
- 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. Previously received any CDK4/6 inhibitor treatment.
3. There are ascites, pleural effusion, pericardial effusion with clinical symptoms at
baseline, those who need drainage, or those who have undergone drainage of serous
effusion within 4 weeks before the first dose.
4. Inability to swallow, intestinal obstruction or other factors affecting the
administration and absorption of the drug.
5. Received systemic therapy such as chemotherapy, molecular targeted therapy or other
clinical trial drugs within 4 weeks before enrollment; received endocrine therapy
within 2 weeks before enrollment.
6. 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).
7. Have undergone major surgical procedures or significant trauma within 4 weeks prior to
randomization, or are expected to undergo major surgery.
8. Pregnant women, lactating female, or women of childbearing age who are unwilling to
take effective contraceptive measures.
9. Have a history of allergies to the drug components of this regimen.
10. 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).
11. History of immunodeficiency, including HIV positive, or other acquired or congenital
immunodeficiency disease, history of organ transplantation.
12. 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.
13. Female patients who are pregnancy, lactation or women who are of childbearing
potential tested positive in baseline pregnancy test.
14. Childbearing female who refuse to accept any contraception practice.
15. 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.).
16. History of neurological or psychiatric disorders, including epilepsy or dementia.
17. 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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