Abstract PD2-08: Ribociclib with endocrine therapy for premenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer: Biomarker analyses from the phase III randomized MONALEESA-7 trial
Authors: Bardia A , Colleoni M , Campos-Gomez S , Jung KH , Wheatley-Price P , Kümmel S , Srimuninnimit V , Taylor D , Im Y-H , Hughes G , Diaz-Padilla I , Miller M , Su F , Tripathy D 
Published: May 2019

Abstract
Background: In the MONALEESA-7 study (NCT02278120), ribociclib (RIB) + a non-steroidal aromatase inhibitor (NSAI)/tamoxifen (TAM) + goserelin (GOS) significantly improved progression-free survival (PFS) vs placebo (PBO) + NSAI/TAM + GOS in premenopausal patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC; hazard ratio 0.553; 95% confidence interval [CI] 0.441–0.694; p=0.0000000983). Here we present PFS data by baseline (prior to study treatment) tumor (primary and metastatic) Ki67, total Rb, and p16 protein expression, and CCND1 (cyclin D1), CDKN2A (p16), and ESR1 (estrogen receptor) messenger RNA (mRNA) levels.
Methods: Pre-/perimenopausal pts (N=672; ≤1 line of prior chemotherapy and no prior endocrine therapy for ABC) were randomized 1:1 to either RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + an NSAI (letrozole [2.5 mg/day]/anastrozole [1 mg/day]) or TAM (20 mg/day) + GOS (3.6 mg every 28 days). The primary endpoint was local PFS, while correlation with biomarker expression was an exploratory endpoint. Baseline tumor tissue was evaluated for Ki67, Rb, and p16 protein expression by immunohistochemistry and CCND1, CDKN2A, and ESR1 gene expression by NanoString® nCounter. To assess correlations between protein/gene expression and PFS, pts were classified into prespecified low vs high expression subgroups; 14% of positively stained cells was used as a cutoff for Ki67, 10th percentile was used as a cutoff for total Rb, and median expression was used as a cutoff for all other proteins/genes.
Results: Based on a data cutoff of August 20, 2017, PFS hazard ratios for most biomarker subgroups favored RIB + NSAI/TAM + GOS vs PBO + NSAI/TAM + GOS (Table).
RIB + NSAI/TAMPBO + NSAI/TAM Events, n/NMedian PFS, monthsEvents, n/NMedian PFS, monthsHazard ratio; 95% CIKi67Low16/5627.522/49Not reached0.523; 0.270–1.013High52/11719.471/11712.60.495; 0.341–0.719Total RbLow8/1927.54/12Not reached0.239; 0.034–1.667High63/15123.889/15212.90.483; 0.342–0.681p16Low28/85Not reached41/7916.40.570; 0.348–0.935High35/7423.847/749.10.403; 0.250–0.651CCND1Low40/8819.151/9213.60.672; 0.442–1.022High36/9723.847/8314.60.381; 0.236–0.614CDKN2ALow29/85Not reached53/9515.60.476; 0.300–0.756High47/10019.445/8012.60.485; 0.310–0.758ESR1Low42/9722.145/8312.90.571; 0.362–0.901High34/8827.553/9214.60.568; 0.359–0.899
It is difficult to draw conclusions for total Rb protein expression due to the small sample size and limited number of events. RIB treatment benefit was numerically greater in pts with high vs low CCND1 mRNA expression levels.
Conclusions: Generally consistent PFS benefits with RIB + NSAI/TAM + GOS vs PBO + NSAI/TAM + GOS were observed irrespective of baseline biomarker expression in cell cycle- and proliferation-related genes. Updated results will be presented at the meeting.
Citation Format: Bardia A, Colleoni M, Campos-Gomez S, Jung KH, Wheatley-Price P, Kümmel S, Srimuninnimit V, Taylor D, Im Y-H, Hughes G, Diaz-Padilla I, Miller M, Su F, Tripathy D. Ribociclib with endocrine therapy for premenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer: Biomarker analyses from the phase III randomized MONALEESA-7 trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD2-08.