Background:Endocrine therapy (ET) with ovarian function suppression is an established first-line treatment for pre- and peri-menopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). Addition of ribociclib (orally bioavailable, selective cyclin-dependent kinase [CDK] 4/6 inhibitor) to first-line ET prolonged progression-free survival (PFS) in a Phase III trial of postmenopausal women with HR+, HER2– ABC (MONALEESA-2). Here we report results from MONALEESA-7 (NCT02278120), the first double-blind, randomized, Phase III trial evaluating ribociclib + tamoxifen/non-steroidal aromatase inhibitor (NSAI) and goserelin specifically in pre- and peri-menopausal patients. Methods: Pre- or peri-menopausal women with HR+, HER2– ABC who had received ≤1 line of chemotherapy and no prior ET for ABC were randomized (1:1) to ribociclib (600 mg/day, 3-weeks-on/1-week-off) or placebo in combination with either tamoxifen (20 mg/day) or an NSAI (letrozole [2.5 mg/day] or anastrozole [1 mg/day]) + goserelin (3.6 mg every 28 days). The primary endpoint was locally assessed PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and safety. Results: 672 patients were enrolled. Baseline patient characteristics were balanced between treatment arms. The primary analysis was conducted after 318 events had occurred; median time from randomization to data cut-off date was 19.2 months. The study met its primary objective: PFS was significantly improved in the ribociclib arm (median PFS = 23.8 months; 95% CI: 19.2–not reached) vs the placebo arm (median PFS = 13.0 months; 95% CI: 11.0–16.4), with a hazard ratio of 0.553 (95% CI: 0.441–0.694; p=9.83×10–8). Subgroup analyses demonstrated consistent PFS benefits for ribociclib vs placebo. In patients with measurable disease at baseline, ORR was 51% vs 36% (ribociclib vs placebo arm; p=3.17×10–4) and CBR was 80% vs 67% (p=3.40×10–4). The most frequent all-grade adverse events (Aes; ≥25% of patients; ribociclib vs placebo arm) were neutropenia (76% vs 8%), hot flush (34% vs 34%), nausea (32% vs 20%), leukopenia (31% vs 6%), and arthralgia (30% vs 27%). Of these, neutropenia (61% vs 4%) and leukopenia (14% vs 1%) were the only Grade 3/4 events reported in ≥5% of patients (ribociclib vs placebo arm). Febrile neutropenia (ribociclib vs placebo arm) occurred in 2% vs <1% of patients. Grade 3/4 QT prolongation (ribociclib vs placebo arm) was reported in 1% vs <1% of patients. Aes leading to permanent discontinuation of ribociclib + tamoxifen/NSAI + goserelin vs placebo + tamoxifen/NSAI + goserelin occurred in 4% vs 3% of patients. Conclusions: MONALEESA-7, the first dedicated trial investigating a CDK4/6 inhibitor in pre- and peri-menopausal women with HR+, HER2– ABC, demonstrated that addition of ribociclib to first-line ET (tamoxifen/NSAI + goserelin) significantly prolonged PFS and had a manageable safety profile. The trial validates the clinical utility of ribociclib with multiple endocrine therapies, including tamoxifen, in premenopausal women with HR+, HER2– ABC. Citation Format: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial [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 GS2-05.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.