2859 - Ribociclib (RIB) + fulvestrant (FUL) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): MONALEESA-3 biomarker analyses

Background

In the Phase III MONALEESA-3 study (NCT02422615), RIB + FUL significantly improved progression-free survival (PFS) vs placebo (PBO) + FUL in patients with HR+, HER2– ABC who received no or up to 1 line of prior endocrine therapy for ABC (hazard ratio 0.593; 95% confidence interval 0.480–0.732). Here we present PFS data by baseline tumor Ki67, total Rb, and p16 protein expression, and CCND1, CDKN2A, and ESR1 messenger RNA (mRNA) levels.

Methods

Postmenopausal women (N = 726) with HR+, HER2– ABC were randomized 2:1 to RIB (600 mg/day; 3 weeks on/1 week off) + FUL (500 mg) or PBO + FUL. The primary endpoint was PFS. PFS by biomarker expression was an exploratory endpoint. Baseline tumor tissue was evaluated for protein expression (immunohistochemistry) and gene expression (NanoString® nCounter Customized Panel). To assess correlations between protein/gene expression and PFS, patients were classified into prespecified low vs high expression subgroups; 14% of positively stained cells was used as a cutoff for Ki67, 10^th percentile was used as a cutoff for total Rb, and median expression was used as a cutoff for all other proteins/genes.

Results

PFS hazard ratios for all biomarker subgroups favored RIB + FUL vs PBO + FUL (Table). Consistent RIB + FUL treatment benefit was seen regardless of Ki67 protein expression or CCND1 gene expression. A numerically greater PFS benefit was observed with RIB + FUL in patients with low vs high p16 protein expression and low vs high CDKN2A mRNA expression; a similar trend was observed in patients with low vs high ESR1 mRNA expression.Table: 346P

Conclusions

RIB + FUL significantly prolonged PFS vs PBO + FUL, with consistent treatment effects observed regardless of biomarker expression. There was a trend towards greater PFS benefit with RIB + FUL in patients with low vs high expression of p16 protein, and low vs high CDKN2A and ESR1 mRNA levels.

Clinical trial identification

NCT02422615 April 21, 2015.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Editorial Acknowledgement

Editorial assistance was provided by Kate Gaffey PhD of ArticulateScience Ltd.

Disclosure

K. Petrakova: Consulting/advisory role, speaker's bureau, travel/accommodation and expenses: Roche, Pfizer and Novartis during the conduct of the study. G. Jerusalem: Grants and personal fees from Novartis during the conduct of the study; Grants, personal fees and non-financial support: Novartis, Roche, BMS; Personal fees and non-financial support: Lilly; Personal fees: Celgene, Pfizer, Puma, Daiichi-Sankyo; Grants and personal fees: Amgen; Grants: MSD; Personal fees and non-financial support from AstraZeneca outside the submitted work. G.S. Sonke: Institutional reimbursement for patient accrual: Novartis during the conduct of the study; Institutional reimbursement for education and steering committee activities: Novartis; Institutional research support: Merck, AstraZeneca, and Roche, outside the submitted work. S. Chia: Honoraria and research funding: Novartis and Roche; Research funding: BMS and Genetech. W. He: Employment: Novartis. K. Rodriguez Lorenc, F. Su: Novartis Employee and owns stock: Novartis. S-A. Im: Advisory role: Novartis, during the conduct of the study; Grants: AstraZeneca; Advisory role: Hanmi, Roche and Pfizer, outside the submitted work. All other authors have declared no conflicts of interest.