tailoring neoadjuvant therapy in hormone receptor positive, her2 negative, luminal breast cancer.

Conditions: Breast Neoplasms

Summary: 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 ≥1%).

Eligibility criteria:
inclusion criteria: * postmenopausal women presenting with histological proven (core biopsy material) hormone receptor positive (er≥50%, pr any), her2 negative, stage ii/ iii breast cancer. * 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 unl * 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 following criteria: * registration in the neolbc trial before 2 weeks biopsy * use of letrozole * outcome central ki67 determination in two weeks biopsy available. exclusion criteria: * 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, soy) * 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 cyp3a4/5. * 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.

Keywords: breast cancer ribociclib letrozole chemotherapy cdk4 cdk6 ki67 neolbc