Abstract P1-15-01: A randomized phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally-advanced hormone-receptor-positive breast cancer: First results
Authors: Quenel-Tueux N , Dalenc F , Bachelot T , Pulido M , Bonnefoi H , Mauriac L , Madranges N , Iggo R , Lortal B , Tunon de Lara C , Campo P , Debled M 
Published: August 2014

Abstract
Background: Neoadjuvant endocrine therapy improves surgical outcomes for postmenopausal women with hormone-receptor-positive (HR+) breast cancer. We performed a prospective trial aiming to assess the response rate of an aromatase inhibitor (anastrozole) or an antiestrogen (fulvestrant) and to better understand the mechanisms of sensitivity or resistance to therapy. Translational research was carried out on DNA and mRNA from samples taken from the tumor at baseline and surgery.
Patients and methods: 120 post-menopausal patients (pts) from 3 centers were enrolled in this multicenter randomized phase II study between Jan 2008 to Aug 2012. They were randomly assigned to receive either neoadjuvant anastrozole (arm A: 1 mg/day) or fulvestrant (arm B: 500 mg with a loading dose during the first month then q4W) for 6 months. The primary endpoint was objective response rate (ORR) determined by clinical palpation based on RECIST criteria at 6 months. Secondary endpoints include ORR by ultrasound and mammography, toxicity, rate of breast-conserving surgery (BCS), pathological response using the Sataloff classification, and disease-free and overall survivals (DFS, OS). Follow-up is planned for 5 years.
Results: 118 pts were evaluable for toxicity. 108 pts were evaluable for response (arm A: 56, Arm B: 52). Baseline characteristics in arm A vs. arm B were well balanced: median age (69 vs. 71yrs), median clinical size (45 vs. 50 mm), histologic grades I-II (56 pts, 91.8% vs. 52 pts, 88.2%), grade III (3 pts, 4.9% vs. 5 pts, 8.5%), and HER2-positivity (4 pts, 6.6% vs. 3 pts, 5.1%).
The most common Grade 1-2 treatment-related toxicities were hot flushes (21.7% and 17.2% in arms A and B respectively), asthenia (10.0% vs. 29.3%) and musculoskeletal symptoms (38.3% vs. 20.7%). Grade 3 Toxicity was reported for one pt (joint pain) in arm A and 3 pts (hot flushes) in arm B. No treatment-related serious adverse events were reported.
ORR was 58.9% (95%CI[45-72]) in arm A and 53.8% (95%CI[39-68]) in arm B; 33 pts in arm A underwent BCS (58.9%) vs. 26 (50%) in arm B. 1 pt in arm A and 3 pts in arm B did not undergo surgery.
TA and TB pathological responses were observed in 24 pts (42.9%) in arm A and 13 pts (25.0%) in arm B. Ki67 values were analyzed before treatment and at surgery in 39 cases (arm A) and 34 cases (arm B). We observed a decrease of Ki67 in 76.9% of pts in arm A and 73.5% in arm B.
Genomic analysis showing the appearance of acquired changes after treatment will be reported in another presentation.
Conclusions: Both anastrozole and fulvestrant seem to be effective neoadjuvant endocrine therapies and may offer an attractive option with low toxicity profile for HR+ post-menopausal women. Both treatments have similar efficacy in terms of both clinical impact and Ki67 decrease.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-15-01.