Longitudinal circulating tumor DNA (ctDNA) analysis in the phase 1b MONALEESASIA study of ribociclib (RIB) + endocrine therapy (ET) in Asian patients (pts) with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC)

Abstract

Background: The phase 1b MONALEESASIA (NCT02333370) study is assessing Asian pts with HR+/HER2– ABC treated with RIB plus ET. We report the results of a longitudinal analysis of ctDNA in this trial. Methods: MONALEESASIA included dose-escalation and -expansion phases and enrolled premenopausal and postmenopausal Japanese pts and postmenopausal Asian non-Japanese pts. In the dose-escalation phase, all pts received RIB + letrozole (LET). In the dose-expansion phase, all Asian non-Japanese pts received RIB + LET, whereas Japanese pts received RIB + LET or fulvestrant (for postmenopausal pts) or RIB + TAM + goserelin (for premenopausal pts). Cell-free DNA (cfDNA) samples were collected from pts at baseline (BL), during treatment, and at end of treatment (EOT). ctDNA was evaluated with a targeted NGS panel comprising ≈ 600 cancer-related genes. ctDNA levels were evaluated throughout treatment by best overall response (BOR). Results: 86 pts were included in this analysis, and 574 cfDNA samples were tested. Some of the most frequently altered genes were PIK3CA, TP53, and ESR1. The alteration frequency for PIK3CA and TP53 was similar from BL to EOT but was numerically higher at EOT for ESR1. There was a consistent trend of lower BL ctDNA levels in pts with partial response (PR) or stable disease (SD) vs pts with progressive disease; however, there was no difference in ctDNA levels at on-treatment time points and EOT by BOR. In all treatment arms, pts with PR and SD had a decrease in ctDNA levels at the first collected on-treatment time point vs BL. Three categories of case studies will be presented: (1) ctDNA was detectable at BL and became undetectable on treatment; (2) ctDNA increased before tumor progression; (3) ctDNA was not detectable throughout treatment. Conclusions: ctDNA levels were dynamic throughout treatment in Asian pts with HR+/HER2– ABC in MONALEESASIA. These findings suggest that on-treatment ctDNA levels may help identify pts at risk of progression.