Trial Outcomes & Findings for Neoadjuvant Study Chemotherapy vs Letrozole + Abemaciclib in HR+/HER2- High/Intermediate Risk Breast Cancer Patients (NCT NCT04293393)

Neoadjuvant Study Chemotherapy vs Letrozole + Abemaciclib in HR+/HER2- High/Intermediate Risk Breast Cancer Patients

Evaluation of the number of patients with a RCB 0-I index as a measure of efficacy. RCB is a continuous variable derived from the primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden. It is estimated from routine pathological sections of the primary breast tumor site and the regional lymph nodes after the completion of Neoadjuvant therapy. The pathological variables include bidimensional diameters of the primary tumor bed, the proportion of primary tumor area containing invasive carcinoma, the number of positive lymph nodes, and the diameter of the largest nodal metastasis

The percentage of decrease in the geometric mean of Ki67 after 2 weeks of treatment in both treatments arms. Number of patients with cell cycle arrest (Ki67 \< 2.7%) after 2 weeks of treatment in both treatment arms.

RCB is classified in four classes based on the residual disease (RD): * RCB-0 defined as pathological complete response. * RCB-I defined as minimal RD. * RCB-II defined as moderate RD. * RCB-III defined as extensive RD.

PEPI requires pathological stage (tumor size and nodal status), level of Ki67 protein, and Allred ER score measured on the surgical specimen. PEPI score 0 includes pT1 or pT2, pN0, Ki67 ≤ 2.7%, Allred score \> 2. Patients with a PEPI score of 0 are found to have a low risk of recurrence.

According to RECIST v1.1 in both treatment arms. Clinical Response Rate (CRR) is defined as the proportion of subjects with complete or partial radiographic response. Complete Response (CR) and Partial Response (PR) definitions are assessed by MRI at baseline and prior to breast surgery, with or without regional lymph nodes surgery, and categorized according to percent reduction in tumor size.

Rate of BCS: defined as the proportion of patients who achieved breast-conserving surgery between both treatment arms.

Invasive event free survival (iEFS): defined as time from randomization to progressive disease or invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause. Invasive disease recurrence is defined as: * Ipsilateral invasive breast tumor recurrence (including second primary invasive breast cancer): an invasive breast cancer involving the same breast parenchyma as the original primary lesion. * Ipsilateral regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, other regional lymph nodes, chest wall, and/or skin of the ipsilateral breast). * Distant recurrence (i.e., evidence of breast cancer in any anatomic site outside local and/or regional location and that has been either histologically confirmed or clinically diagnosed as recurrent invasive breast cancer) * Contralateral invasive breast cancer * Second primary invasive cancer of non-breast origin.

Safety assessments were performed at baseline and during the study: Vital signs assessments (blood pressure, pulse and body temperature), measurement of left ventricular ejection fraction, standard 12-lead electrocardiogram, laboratory assessments (hemoglobin, White Blood Cell, Absolute Neutrophil Count, Lymphocytes, platelet count, fasting glucose, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, serum creatinine, sodium, potassium, total calcium, blood urea nitrogen (or urea), pregnancy test , ophthalmologic assessments (visual acuity testing, slit lamp examination, fundoscopy), Viral serology. AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The toxicity of study treatments will be evaluated in the safety population.

Gene expression data provided by a multigene expression panel in sequential tumor biopsies.