Circulating tumor DNA (ctDNA) and serum thymidine kinase 1 activity (TKa) matched dynamics in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor 2–negative (HER2-) advanced breast cancer (ABC) treated in first-line (1L) with ribociclib (RIB) and letrozole (LET) in the BioItaLEE trial
Journal of Clinical Oncology 40, no. 16_suppl (June 01, 2022) 1012-1012.

Study type/Objective
A multi-center, head-to-head comparison of TKa and ctDNA as predictive biomarkers of response in pts with HR+, HER2− ABC treated with RIB+-LET enrolled in the BioItaLEE trial (NCT03439046), n = 287.

The prognostic/predictive value of both TKa and ctDNA were assessed from baseline and on-treatment cycle 1 blood samples from BioItaLEE. Baseline samples for both ctDNA and TKa were equally prognostic for PFS. Samples from patients with detectable ctDNA or high TKa levels at BL predicted for a shorter mPFS (16.59 mo vs 16.1 mo respectively) than samples from patients with undetectable ctDNA or low TKa (mPFS not reached for both biomarkers). In samples with detectable ctDNA at BL (113/263 or 43%of patients) on-treatment cycle 1 day 15 samples were assessed for clearance of ctDNA. Clearance of ctDNA at D15 was predictive for a greater mPFS (21.85 mo) vs lack of clearance at D15 (12.09 mo, HR 0.51, p=0.0228). Using on-treatment assessments of TKa at D15 and C2D1 from 92% of patients (241/263) allowed for more precise stratification of patients into 3 different prognostic patterns. Additionally, undetectable levels of TKa at both D15 and C2D1 was highly predictive for outcome with a mPFS that was not reached after 27 months of follow-up, versus a mPFS of only 10.1 mo in patients whose on-therapy samples did have detectable TKa (HR 0.18, p=<0.0001) Combining the two biomarkers did not appear to further improve prediction of patients with the best clinical outcome, but did slightly improve identification of patients predicted to have the worst clinical outcome (mPFS 6.65 mo).

These findings suggest that early dynamic assessments of both ctDNA and TKa can predict outcome of pts treated with RIB+LET. On-therapy measurements of TKa offer greater dynamic stratification of patients and additional predictive value versus ctDNA. TKa and ctDNA capture different features of tumor biological activity and both their individual and combined patterns warrant further evaluation in relation to other treatments, settings, and diseases. Clinical trial information: NCT03439046.



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