Abemaciclib and Letrozole with Radiation Prior to Surgery for the Treatment of HR-Positive, HER2-Negative Invasive Breast Cancer, RADIANT Trial

Inclusion Criteria

• Histologically and/or cytologically confirmed diagnosis of invasive (ductal, lobular or mixed histology), cT1-T2N0 disease. Minimum tumor size of 1.5 cm.
• Expression of estrogen receptor (ER) or progesterone receptor (PR) and negative expression of HER2 per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines.
• Oncotype DX Breast Recurrence score of less than 25 on core biopsy specimen.
• Post-menopausal status defined: * Age 60 years or older * Age < 60 with amenorrhea for at least 12 months in the absence of prior chemotherapy, tamoxifen, toremifene, or ovarian suppression and estradiol and follicle-stimulating hormone (FSH) in postmenopausal range.
• No clinical suspicion of metastasis disease. Staging scans may be done per the discretion of the treating physician.
• Eastern Cooperative Oncology group (ECOG) performance status of performance status (PFS) ≤ 2.
• Patients must be eligible to undergo surgery, either lumpectomy or mastectomy for local treatment of the breast cancer. Surgical margins at discretion of surgeon per National Comprehensive Cancer Network (NCCN) guidelines. Axillary exploration at discretion of surgeon but all patients minimally have sentinel lymph node evaluation at time of surgery.
• The patient is able to swallow oral medications.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.
• Platelets ≥ 100 x 10^9/L.
• Hemoglobin ≥ 8 g/dL. * Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN). * Patients with Gilbert's syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
• Synchronous HR positive/HER2- negative breast cancers (unilateral) are allowed as long no other exclusions exist.

Exclusion Criteria

• History of ipsilateral breast cancer.
• Prior treatment with CDK4/6 inhibitors or aromatase inhibitors.
• History of chest wall or ipsilateral breast radiation.
• Inflammatory breast cancer.
• Patient needs neoadjuvant chemotherapy per treating physician.
• Presence of distant metastatic disease.
• Contraindication for surgery.
• Uncontrolled hypertension (systolic blood pressure [bp] > 190 mm Hg or diastolic bp > 100 mm Hg).
• Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
• Life expectancy < 12 weeks.
• Patient who has a history of allergy or hypersensitivity to any of the study drugs.
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance < 30 ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
• The patient has had major surgery within 14 days prior to enrollment.
• The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study.
• The patient has active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]). Screening is not required for enrollment.
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.