P3-15-01: An Interim Efficacy Analysis of Neoadjuvant Letrozole in the New Primary Endocrine-Therapy Origination Study (NEOS/N-SAS BC06): A Randomized Study of Adjuvant Endocrine Therapy with or without Chemotherapy for Postmenopausal Breast Cancer Patients Who Responded to Neoadjuvant Letrozole.

Abstract

Abstract Background It has not been established if adjuvant chemotherapy is required for patients with intermediate-risk endocrine-responsive postmenopausal breast cancer. The NEOS is a randomized controlled trial to verify the necessity of adjuvant chemotherapy in patients with node-negative, ER-positive, and HER2−negative postmenopausal breast cancer who responded to neoadjuvant endocrine therapy. For neoadjuvant letrozole (LET), the protocol specified that an interim analysis should be performed to avoid lack of benefit to patients if no therapeutic effects, which were anticipated before the start of the study, were obtained. Methods: Patients who complied with the eligibility criteria were administered LET preoperatively in weeks 24–28 after primary enrollment. Patients evaluated as complete response (CR), partial response (PR) or stable disease (SD) underwent secondary enrollment and will be divided at random into two arms, an arm given LET for 4.5-5 years after chemotherapy and another arm given only LET for 4.5-5 years. Patients evaluated as progressive disease during LET treatment will receive discretionary treatment. For neoadjuvant LET, the number of patients requiring interim analysis of efficacy was calculated as 140 based on the assumption that the threshold response rate of CR+PR+SD was 75% and its expected response rate was 85% in patients who completed neoadjuvant LET, and that the one-sided level of significance was 5% and the statistical power was 90%. When the hypothesis that the rate of CR+PR+SD was less than 75% was not rejected at a significance level of 5%, the study was discontinued and when it was rejected, the study was continued. Results: As of June 2011, 140 patients in 39 centers had completed neoadjuvant LET. The median age was 64 years old (range: 50–75) and the median Body Mass Index (BMI) was 23.90 (±3.77). According to MRI or CT scan, CR occurred in 2 (1.4%), PR in 57 (40.7%), and SD in 59 patients (42.1%). The rate of CR+PR+SD among the 140 patients was 84.3% (90% confidence interval: 78.6−88.7). In ultrasonography, 47 patients (33.6%) showed a decrease in the long diameter of 30% or more in a mono-dimensional measurement and 52 patients (37.1%) showed a decrease in volume of 50% or more in a three-dimensional measurement. The neoadjuvant LET effects showed no differences in patients with a BMI of less than 20, 20–25, and more than 25. No serious adverse events were observed. Discussion: The rate of patients who achieved CR+PR+SD by neoadjuvant LET complied adequately with the continuation criteria for the study. We will present the results for 205 patients who could be evaluated for efficacy and safety of neoadjuvant LET as of May 2011. This study was supported by Public Health Research Foundation. Clinical Trial Registration Information: UMIN (http://www.umin.ac.jp/), Study ID: 000001090 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-15-01.