Abstract PD2-01: Randomized phase 3 trial of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor positive, node positive early breast cancer: Final efficacy and safety results of the femara versus anastrozole clinical evaluation (Face) trial

Background The FACE trial was designed to evaluate the efficacy and safety of adjuvant letrozole (LET) versus anastrozole (ANA) in postmenopausal patients with hormone receptor-positive (HR+), node-positive breast cancer. Materials and methods In this phase 3b, open-label, multicenter trial, postmenopausal women with HR+ and lymph node positive breast cancer were randomized 1:1 to receive either LET (2.5 mg) or ANA (1 mg) daily for 5 years in the adjuvant setting. Randomization was stratified by the number of lymph nodes (1-3 versus 4+) and HER2 status (positive versus negative). Patients with stage IIA, IIB or IIIA invasive cancer were eligible. Treatment continued for 5 years or until disease recurrence. The primary endpoint was disease free survival (DFS) at 5 years. Key secondary endpoints were safety and overall survival (OS). Results Between Dec 2005 and Mar 2008, 4170 patients were randomized to receive LET (n = 2076) or ANA (n = 2094). Baseline characteristics were generally balanced between the two arms. Median age was 62 years; 71.4% of pts had 1-3+ lymph nodes, and 8.7% of cancers were HER2+. Median duration of exposure was 60 months in both arms. With 709 of the protocol-planned 959 DFS events, 5-yr estimated DFS rate was 84.9% for LET vs. 82.9% for ANA (HR = 0.93 [95% CI: 0.80 – 1.07]; p = 0.3150). 5-yr estimated OS rate was 89.9% for LET vs. 89.2% for ANA (HR = 0.98 [95% CI: 0.82 – 1.17]; p = 0.7916). Primary reasons for treatment discontinuation in the LET versus ANA arms were AEs (15.1% vs. 14.3%) and disease progression (9.5% vs. 10.4%). Safety profiles were similar between treatment arms. The most common adverse events (AEs) in the LET versus ANA arms were arthralgia (48.2% vs. 47.9%), hot flushes (32.5% vs. 32.3%) and fatigue (16.8% vs. 16.6%). Suspected drug-related grade 3/4 AEs were reported in 9.5% of patients in the LET arm versus 8.1% of patients in the ANA arm; suspected drug-related AEs leading to discontinuation were reported in 14.0% vs. 12.9% of patients in LET vs. ANA arms, respectively. Preplanned and exploratory subgroup analyses will be presented. Conclusions Treatment with LET did not demonstrate DFS efficacy difference over ANA in postmenopausal patients with HR+, node-positive breast cancer. (Funded by Novartis; ClinicalTrials.gov number NCT00248170). Citation Format: O9Shaughnessy J, Yardley DA, Burris HA, De Boer R, Amadori D, McIntyre K, Ejlertsen B, Gnant M, Jonat W, Pritchard KI, Dowsett M, Hart L, Poggio S, Valagussa P, Salomon H, Wamil B, Smith I. Randomized phase 3 trial of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor positive, node positive early breast cancer: Final efficacy and safety results of the femara versus anastrozole clinical evaluation (Face) trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD2-01.