Background

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.

Methods

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.

Results

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 2^nd 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: 250P

Conclusions

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.

Legal entity responsible for the study

Kreina Sharela Vega Cano.

Funding

Has not received any funding.

Disclosure

O. Mirallas: Financial Interests, Personal, Invited Speaker: ROVI, Roche; Financial Interests, Institutional, Invited Speaker: Merck; Other, Travel Expenses: Kyowa kirin, Almirall; Other, Travel Expenses and Conference Fee: Sanofi. E. Zamora: Financial Interests, Personal, Invited Speaker, Review session for medical oncologists: Eisai, Lilly; Other, Registration to ESMO Congress 2022 (virtual): Novartis; Other, Registration to: Eisai. M. Cruellas Lapena: Financial Interests, Institutional, Invited Speaker: ROCHE. C. Saura Manich: Financial Interests, Personal, Advisory Board: AX'Consulting, AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd., Gilead, ISSECAM, Lilly, MediTech, Medical Statistics Consulting, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Piere Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, Seagen, Solti, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: AX's Consulting SARL, Boehringer Ingelheim, Bristol Meyers Squibb, INDITEX, Merck Sharp & Dohme España, Novartis, SACE Medhealth SL, Simon Kucher &Partners SL, Genentech, Innoup, Millenium, Sanofi, Seattle Genetics; Financial Interests, Personal, Other, SC: Byondis B.V., German Breast Group, Glaxo, International Breast Cancer Study Group (IBCSG), MacroGenics, Medsir, Menarini, Merus, Merus, Netherlands Cancer Institute (NKI), Queen Mary (University of London), Seagen, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, GlaxoSmithKline, MacroGenics, Immunomedics, Innoup Farma, International Breast Cancer Study Group (IBCSG), Medica Scientia Innovation Research, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics, SOLTI; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), SOLTI group (Academic research group in breast cancer), Geicam (Spanish Breast Cancer Research Group), American Association for Cancer Research (AACR). M. Bellet-Ezquerra: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Lilly, Stemline-Menarini; Other, Speaker'sBureau and Travel Expenses: Pfizer; Other, Speaker's Bureau: Novartis, Lilly. All other authors have declared no conflicts of interest.