250P Liver Toxicity (LT) in patients (pts) with ER-positive HER2-negative metastatic breast cancer (MBC) treated with first-line Cyclin-Dependent Kinase 4/6 inhibitors (CDKi)

Abstract

A meta-analysis of all Ph3 trials with CDKi plus endocrine therapy (ET) has established 13% incidence of LT of any grade (vs 5.4% with ET alone). However, the clinical characteristics of these pts and the predictive factors associated with developing LT remain unknown. All MBC pts treated with first-line CDKi in Vall d’Hebron Hospital from 2018 to 2022 were analyzed retrospectively. LT was defined as ≥G2 AST/ALT elevation. Clinical and laboratory characteristics, oncologic disease status, and evolution of liver function tests for those pts were registered. Among 472 pts treated, 26 (5.5%) developed LT, G2 in 11 (42%), G3 in 13 (50%) and G4 in 2(8%) without LT related-deaths. LT occurred in 3%, 8% and 11.6% of pts receiving palbociclib, abemaciclib and ribociclib, respectively. Baseline characteristics: median (M) age 61y, premenopausal 54%, overweight/obese 59%, 11.5% alcohol consumers, 27% current/former smokers, 27% stage IV de novo and 27% with liver metastases. As for cardiovascular risk factors: 32% had dyslipemia, 31% liver steatosis at CT scan and 26.9% arterial hypertension. Concomitant ET was letrozole 54%, fulvestrant 35% and anastrozole 11%. LT occurred after 7 cycles (M), and 218 days (IQR 37-399). Only 1 pt receiving abemaciclib had G4 bilirubin elevation without fulfilling Hy's Law criteria. In 88.5% LT returned to basal in 44 days (M) (IQR 26-61). CKDi was reintroduced in 58% of pts; 8% at the same dose, 54% at -1 dose level, and 38% at -2 dose level. Of them, 61.5% had a 2nd LT episode which resolved in 62.5% in 26 days (M) (IQR 14-49). The results by type of CDKi are shown in the table. Table: 250PCharacteristicsPalbociclibAbemaciclibRibociclibLT pts/Total pts8/2839/1129/77M days until LT1166398LT resolved87%75%100%M days to resolution282646Relapse of LT20%75%66%M days until relapse142011 Open table in a new tab In our cohort of pts 5.5% developed LT. LT reached G3 in 58% of cases, mainly with ribociclib. A high proportion of those pts had ≥25 BMI and 31% had liver steatosis. LT was mainly reversible with no fatal cases. These results could help to develop prediction scores to identify patients at risk of developing severe LT.