The aim of this prospective, randomized, multicenter, open-label, phase II study is to test
if chemotherapy can be replaced by the combination of ribociclib plus letrozole as a
neo-adjuvant therapy for patients with non-metastatic primary luminal breast cancer.
Based on Ki67 levels after two weeks of initial letrozole treatment in postmenopausal
patients with hormone receptor positive, HER2 negative, stage II/III breast cancer, patients
are either advised to continue letrozole treatment (if Ki67 <1%) or will be randomized
between standard chemotherapy (AC-T) or ribociclib in combination with letrozole (if Ki67
- Postmenopausal women presenting with histological proven (core biopsy material)
hormone receptor positive (ER≥50%, PR any), HER2 negative, stage II/ III breast
- Measurable disease (breast and/or lymph nodes)
- WHO 0-2
- Adequate bone marrow function (within 4 weeks prior to registration): WBC≥3.0x109/l,
neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
- Adequate liver function (within 4 weeks prior to registration): bilirubin ≤1.5 x upper
limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x
- Adequate renal function (within 4 weeks prior to registration): the calculated
creatinine clearance should be ≥50 ml/min
- Accessible for treatment and follow-up
- Written informed consent
Inclusion criteria randomization specific:
In order to be eligible to be randomized in this study, a subject must meet all of the
- Registration in the NEOLBC trial before 2 weeks biopsy
- Use of letrozole
- Outcome central Ki67 determination in two weeks biopsy available.
- Evidence of distant metastases (M1)
- Previous invasive breast cancer
- Prior chemotherapy, radiation therapy or hormonal therapy with the exception of
patients who received letrozole ≤ 14 days (+ max. 4 days) prior to registration and
who are still on letrozole.
- Previous malignancy within 5 years, with exception of a history of a previous basal
cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
- Peripheral neuropathy > grade 2, whatever the cause
- Serious other diseases as infections (hepatitis B, C and HIV), recent myocardial
infarction, clinical signs of cardiac failure or clinically significant arrhythmias or
on screening, any of the following cardiac parameters: bradycardia (heart rate <50 at
rest) or QTcF ≥450 msec.
- Known hypersensitivity reaction to any of the components of the treatment (peanuts,
- Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment,
prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH),
or fondaparinux is allowed.
- Currently receiving any of the following substances and cannot be discontinued 7 days
prior to randomisation:
- Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit
hybrids, pummelo's, star-fruit, pomegranate and Seville oranges.
- That have a known risk to prolong the QT interval or induce Torsades de Pointes.
- That have a narrow therapeutic window and are predominantly metabolized through
- Herbal preparations/medications, dietary supplements.
- Medical or psychological condition which in the opinion of the investigator would not
permit the patient to complete the study or sign meaningful informed consent.