Abstract P4-22-05: First-line ribociclib plus letrozole in patients with de novo HR+, HER2– advanced breast cancer (ABC): A subgroup analysis of the MONALEESA-2 trial
Authors: O'Shaughnessy J , Petrakova K , Sonke GS , André F , Conte P , Arteaga CL , Cameron DA , Hart LL , Villanueva C , Jakobsen EH , Lindquist D , Souami F , Li X , Germa C , Hirawat S , Hortobagyi GN 
Published: March 2017

Abstract
Background: Around 15,000 US patients per year are diagnosed with de novo ABC. Due to the absence of prior systemic treatment for breast cancer, tumors of patients with de novo ABC may exhibit a different disease biology, which could result in different tumor responses compared with patients who have relapsed breast cancer. Ribociclib is an orally bioavailable cyclin-dependent kinase (CDK) 4/6 inhibitor. Results from MONALEESA-2, a double-blind, placebo-controlled, randomized Phase 3 trial (NCT01958021), demonstrated that first-line therapy with ribociclib + letrozole significantly improved progression-free survival (PFS) vs placebo + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) ABC. Many patients with de novo ABC receive endocrine therapy in the first line and in subsequent lines; here we present results from the MONALEESA-2 study in a subpopulation of patients with de novo ABC.
Methods: Postmenopausal women (N=668) with HR+, HER2– ABC who had no prior systemic therapy for ABC were randomized 1:1 (stratified by liver and/or lung metastases) to receive ribociclib (600 mg/day; 3-weeks-on/1-week-off) + letrozole (2.5 mg/day; continuous) or placebo + letrozole. Patients with de novo ABC were eligible. Additional eligibility criteria included measurable disease or ≥1 predominantly lytic bone lesion, Eastern Cooperative Oncology Group performance status ≤1, and adequate bone marrow/organ function. Prior CDK4/6 inhibitors or systemic therapy for ABC were prohibited. Patients may have received ≤14 days of letrozole or anastrozole for ABC. The primary endpoint was locally assessed PFS; a predefined subgroup analysis evaluated PFS in patients with de novo ABC.
Results: In total, 227 patients with de novo ABC were enrolled. Patients with de novo ABC were equally distributed with 114 (34%) and 113 (34%) in the ribociclib + letrozole and placebo + letrozole arms, respectively. Median duration of exposure to study treatment in the ribociclib + letrozole vs placebo + letrozole arms was 14.1 vs 12.8 months. Treatment was discontinued in 84 (37%) patients with de novo ABC (ribociclib + letrozole vs placebo + letrozole, n [%]; 34 [30%] vs 50 [44%]). Reasons for treatment discontinuation (ribociclib + letrozole vs placebo + letrozole, n [%]) included disease progression (21 [18%] vs 41 [36%]), patient/physician decision (5 [4%] vs 6 [5%]), and adverse events (6 [5%] vs 3 [3%]). PFS was increased in patients with de novo ABC who received ribociclib + letrozole vs placebo + letrozole (hazard ratio=0.448 [95% confidence interval: 0.267–0.750]). The 12-month PFS event-free probability in patients with de novo ABC was 82% in the ribociclib + letrozole arm vs 66% in the placebo + letrozole arm.
Conclusions: The combination of ribociclib + letrozole significantly improved PFS compared with placebo + letrozole in postmenopausal women with HR+, HER2– de novo ABC at diagnosis and therefore may become an important treatment option in the de novo ABC setting.
Keywords: Advanced breast cancer; CDK4/6 inhibitor; Letrozole; Ribociclib
Citation Format: O'Shaughnessy J, Petrakova K, Sonke GS, André F, Conte P, Arteaga CL, Cameron DA, Hart LL, Villanueva C, Jakobsen EH, Lindquist D, Souami F, Li X, Germa C, Hirawat S, Hortobagyi GN. First-line ribociclib plus letrozole in patients with de novo HR+, HER2– advanced breast cancer (ABC): A subgroup analysis of the MONALEESA-2 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-05.