Biomarker analyses of Asian women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) receiving ribociclib (RIB) + endocrine therapy (ET)

Abstract

Background: The ongoing Phase Ib MONALEESASIA (NCT02333370) study is a doseescalation (RIB + letrozole [LET]) and dose-expansion (RIB + LET, fulvestrant [FUL], or tamoxifen [TAM]) study in Asian patients (pts) with HR+, HER2- ABC; here we present biomarker analyses. Methods: In the dose escalation, postmenopausal pts with HR+, HER2- ABC (no prior therapy for ABC) received RIB (300, 400, or 600 mg/day [d]; 3 weeks on/1 week off) + LET (2.5 mg/d). In the dose expansion, pre- and postmenopausal pts (≤1 line of any prior therapy for ABC) received RIB (recommended Phase II dose) + LET (2.5 mg/d), FUL (500 mg, d1 and 15 of Cycle [C] 1, then every 28 d), or TAM (20 mg/d) + goserelin (3.6 mg every 28 d; premenopausal pts only). Baseline (BL) and on-treatment (OT; collected at d15 of C1) samples were assessed for dynamic changes in messenger RNA expression (NanoString 230- gene nCounter® GX Human Cancer Reference panel). Differences in gene expression between pre- and postmenopausal pts were assessed using a Mann-Whitney-Wilcoxon test. Results: As of Mar 2, 2018, BL tumor mRNA expression was evaluated in 68 of 88 pts. Dynamic gene expression changes were assessed in 5 pts with paired BL/OT samples, with an observed decrease in mRNA expression of E2F-responsive (e.g. E2F1, MYC, and TYMS) and cell cycle-related genes (e.g. CDK genes). Super responders (n = 5; no progression ≥24 months post-randomization) and poor responders (n = 6; progressed ≤8 weeks postrandomization) showed differential expression of cell cycle-, proliferation-, and breast cancer-related genes. Genes with different expression levels between pre- (n = 9) and postmenopausal Japanese pts (n = 31) were identified. BL circulating tumor DNA analysis by next-generating sequencing (n = 82) will be presented. Conclusions: In Asian pts with HR+, HER2- ABC, suppression of pharmacodynamic biomarker gene expression, including E2F-responsive genes, indicated that RIB + ET inhibited the intended targets. Differences in BL gene expression patterns were observed between pts with sustained responses vs those who progressed ≤2 treatment cycles. Due to small pt numbers, further investigation is needed.