NoLEEta

Main inclusion criteria:

• Patient is female, ≥ 18 years old, with known menopausal status
• ECOG performance status 0 to 1
• Histologically confirmed invasive breast carcinoma:
  • Pathological stage (8th edition of the AJCC), including pT2 pN0 Grade 3 or pT2 pN0 Grade 2 with Ki67≥20% or pT0-2 pN1 or pT3-4 pN0
    ER-positive (≥10%) and HER2-negative
• Chemotherapy eligible per investigator decision
• No contraindication for the adjuvant endocrine therapy (ET) or chemotherapy.
• Curative surgery within 12 weeks before randomization.
• Women of childbearing potential must have a confirmed negative serum pregnancy test (β-hCG) and agree to use one effective form of contraception.
• Adequate hematological, renal, and hepatic function.
• Standard 12-lead ECG values assessed, as:
• QTcF interval at screening < 450 milliseconds
• Resting heart rate 50-100 beats per minute

Main exclusion criteria:

• Has received any neoadjuvant chemotherapy or any prior CDK4/6 inhibitor.
• Breast cancer diagnosed while patient was receiving tamoxifen, raloxifene or aromatase inhibitors within the last 2 years prior to randomization.
• Known hypersensitivity to any of the excipients of ribociclib and/or ET.
• Evidence or history of distant metastases of breast cancer, inflammatory breast cancer, breast cancer recurrence or a different primary breast cancer.
• Concurrent or prior invasive malignancy whose treatment was completed within 2 years before randomization.
• Breast cancer that is considered as endocrine therapy insensitive.
• Major surgery within 14 days prior to study treatment initiation.
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
• Presence of any other (concurrent severe and/or uncontrolled) medical conditions, physical examination findings or laboratory results that raise reasonable suspicion of a contraindication for study participation.
• Previous history of pneumonitis.
• Currently receiving any of the following substances within 7 days before randomization and which cannot be stopped:
• Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit, pummelos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4/5
• Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
• Any medication prohibited according to the instructions for goserelin, leuprolide or triptorelin (pre-menopausal patients), anastrozole, exemestane, letrozole, or ribociclib.
• Medications known to have a risk of prolonging the QT interval or causing Torsades de Pointes.
• Concurrently using hormone replacement therapy. Estrogen replacement therapy discontinued less than two weeks prior to the start of treatment.
• Currently receiving or having received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment, or not fully recovered from side effects of such treatment (see protocol for exceptions).