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

Abstract

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. Method(s): 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 (NanoStringnCounter 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, 10th percentile was used as a cutoff for total Rb, and median expression was used as a cutoff for all other proteins/genes. Result(s): 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. Conclusion(s): 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.