199P Correlation of circulating tumor DNA (ctDNA) or thymidine kinase activity (TKa) dynamic patterns with tumor response in patients (pts) with hormone receptor (HR)+ human epidermal growth factor 2 (HER2)– advanced breast cancer (ABC) on ribociclib (RIB) + letrozole (LET) in BioItaLEE trial

Early dynamic patterns (DP) of ctDNA and TKa provide improved prediction of progression free survival for pts with HR+ HER2− ABC treated with RIB+LET enrolled in the BioItaLEE trial. Here we evaluate their association with tumor response. Of the 287 pts enrolled, 236 with post-baseline imaging evaluation were included in the present analyses. Clinical benefit rate (CBR) was defined according to Recist Critera 1.1. According to presence or absence of MUT ctDNA at cycle (C)1 day (D)1 and C1D15, ctDNA DP were defined as: Confirmed Wild Type (WT) (WT/WT), New mutated (MUT) (WT/MUT), Cleared (MUT/WT), confirmed MUT (MUT/MUT). TKa DP were defined as TKa inhibited (INH; +/-/-), rebounded (+/-/+) and insufficiently INH (+/+/+) according to the presence (+) or absence (-) of TKa at C1D1, C1D15 and C2D1. Multivariate logistic regression models adjusting for pts status, tumor type, visceral metastases and number of organs involved were used to correlate CBR with ctDNA and TKa dynamics. Overall CBR was 73.3%. CBR according to ctDNA and TKa DP is shown in the table. In the logistic model, MUT/MUT vs WT/WT pts had an Odds Ratio (OR) of 0.42 (p=0.033). OR of TKa rebounded vs. TKa INH pts and TKa insufficiently INH vs. TKa INH pts were 0.38 (p=0.019) and 0.24 (p=0.008) respectively (Table). Table: 199PLogistic modelCBR (%)OR (95% CI) p-valuectDNA DP (n)WT/WT (105)80ReferenceWT/MUT (17)710.48 (0.15; 1.57) 0.226MUT/WT (47)680.44 (0.20; 1.00) 0.050MUT/MUT (50)660.42 (0.19; 0.93) 0.033TKa DP (n)INH (60)85ReferenceRebounded (128)690.38 (0.17; 0.85) 0.019Insufficiently INH (31)610.24 (0.08; 0.69) 0.008 Open table in a new tab DP of either ctDNA and TKa were associated with tumor response to RIB+LET. Our data suggest that insufficient inhibition of TKa at C1D15 may be a surrogate marker for tumor progression. If further confirmed, TKa measurement may be helpful for patients needing a rapid evaluation of tumor response.