Trilaciclib in Patients With Early-Stage HR-negative Breast Cancer Receiving Adjuvant Chemotherapy

Inclusion criteria

• age ≥ 18 years;
• breast cancer meets the following criteria:

• Histologically or cytologically confirmed and adequately resected non-metastatic primary invasive breast cancer;
• Cohort A only: ER, PR negative (< 1% nuclear staining as assessed by immunohistochemistry [IHC]), HER2 negative (HER2/CEP17 ratio < 2.0 or mean HER2 gene copy number < 4 signals/nucleus detected by IHC 0 or 1 + or in situ hybridization [ISH]); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were HR negative/HER2 negative.
• Cohort B only: ER, PR negative (< 1% nuclear staining as assessed by immunohistochemistry [IHC]); HER2 positive: HER2/CEP17 ratio ≥ 2.0 or HER2 gene copy number ≥ 4 signals/nucleus detected by IHC 3 + and ISH; HER2 gene copy number ≥ 6 signals/nucleus detected by IHC 3 + or 2 + and ISH); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were HR negative/HER2 positive.
• Subjects must have positive lymph nodes or tumors > 2 cm;
• The interval between radical surgery and the first dose ≤ 60 days;
• Eastern Cooperative Oncology Group (ECOG) performance score 0-1;
• have appropriate organ function, meet the following criteria: (1) have appropriate bone marrow function: Hb ≥ 100 g/L (no ESA and blood transfusion within 14 days before the first dose); absolute neutrophil count (ANC) ≥ 2 × 10^9/L (no G-CSF within 14 days before the first dose); platelet count ≥ 100 × 10^9/L (no rhTPO/rhIL-11 and platelet transfusion within 14 days before the first dose); (2) appropriate liver and kidney function: alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN, serum creatinine ≤ 1.5 × ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula); (3) appropriate cardiac function: left ventricular ejection fraction (LVEF) ≥ 55%;
• Non-hematologic toxicities from prior surgical procedures recovered to ≤ Grade 1 or baseline (except alopecia);
• Females of childbearing potential agree to practice reliable contraception during the clinical trial and have a negative serum or urine pregnancy test within 7 days prior to dosing;
• Voluntarily join this study and sign informed consent, have good compliance and are willing to cooperate with follow-up.

Exclusion criteria

• Prior neoadjuvant therapy (including chemotherapy, targeted therapy, immunotherapy, or radiotherapy);
• History of other malignancy within 5 years prior to first dose, except basal cell carcinoma and cervical carcinoma in situ;
• Any T4 or N2 or known N3 or M1 breast cancer;
• Subjects who cannot receive or tolerate postoperative chemotherapy for various reasons;
• Heart disease ineligible for epirubicin, docetaxel, trastuzumab/pertuzumab:

• Any documented history of myocardial infarction, congestive heart failure
• Angina pectoris requiring antianginal medication
• Grade 3 or 4 cardiac arrhythmia (NCI CTCAEv5.0)
• Clinically significant valvular heart disease;
• Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
• Known history of hypersensitivity to the drug components of this protocol;
• Any other condition that, in the opinion of the investigator, would make the patient inappropriate for participation in this study.