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.