Abstract OT3-05-06: EarLEE-2: A phase 3 study of ribociclib + endocrine therapy (ET) for adjuvant treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–), intermediate-risk, early breast cancer (EBC)
Authors: O'Shaughnessy J , Alba E , Bardia A , Dent S , Dieras V , Hortobagyi G , Im S-A , Montemurro F , Untch M , Yardley DA , Chakravartty A , Germa C , Miller M , Slamon D 
Published: February 2018

Abstract
Background: Adjuvant ET with or without chemotherapy reduces the risk for recurrence of HR+, HER2– EBC. However, recurrence is still common, especially in patients with adverse clinical and pathologic features. In the phase 3 MONALEESA-2 trial, the cyclin-dependent kinase 4/6 inhibitor ribociclib (LEE011), in combination with letrozole, prolonged progression-free survival versus letrozole plus placebo in postmenopausal women with HR+, HER2– advanced breast cancer and no prior therapy for advanced disease (HR = 0.56, 95% CI, 0.43-0.72; P = 3.29×10−6; Hortobagyi et al. N Engl J Med. 2016). EarLEE-2 is investigating the efficacy and safety of ribociclib with ET versus placebo with ET as adjuvant treatment in patients with intermediate-risk EBC.
Trial design: In this double-blind, placebo-controlled, phase 3 adjuvant trial, ˜4,000 women and men with fully resected, intermediate-risk, HR+, HER2– EBC (defined as AJCC 8th ed. Prognostic Stage Group II) are being randomized 1:1 to oral ribociclib (600 mg/day, 3 weeks on/1 week off for ˜24 months) plus ET or to placebo plus ET. Adjuvant ET may include tamoxifen, letrozole, anastrozole, or exemestane for ≥ 60 months with ovarian suppression for premenopausal women at the discretion of the investigator. Adjuvant ET in men will be tamoxifen only. Neoadjuvant therapy is not permitted. Randomization is stratified by menopausal status (men and premenopausal women vs postmenopausal women), prior adjuvant chemotherapy (yes vs no), Prognostic Stage Group (IIA vs IIB), and geographic region (North America/Europe/Australia vs rest of the world). Eligible patients must have tumor tissue from the surgical specimen, adequate bone marrow and organ functions, normal serum electrolytes, QTc interval &lt; 450 msec, and completed and recovered from acute toxicities of adjuvant radiotherapy and/or chemotherapy. The primary endpoint is invasive disease-free survival (per STEEP system; Hudis et al. J Clin Oncol. 2007). Secondary endpoints include recurrence-free survival, distant disease-free survival, overall survival, quality of life, and safety. Global recruitment to EarLEE-2 is ongoing. NCT03081234
Citation Format: O'Shaughnessy J, Alba E, Bardia A, Dent S, Dieras V, Hortobagyi G, Im S-A, Montemurro F, Untch M, Yardley DA, Chakravartty A, Germa C, Miller M, Slamon D. EarLEE-2: A phase 3 study of ribociclib + endocrine therapy (ET) for adjuvant treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–), intermediate-risk, early breast cancer (EBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-05-06.