First line combination of ribociclib and letrozole in patients (pts) with metastatic breast cancer (MBC): Focus on hepatic toxicity in the context of a real-world setting the Italian, multicenter Hermione-8 study

e13064 Background: The introduction in the clinical practice of CDK4 / 6 inhibitors, in combination with endocrine therapy, has been a breakthrough in the therapeutic scenario of hormone receptor+ve/Human Epidermal growth Factor 2–ve (HR+/HER2–) MBC pts. However, despite the outstanding results in terms of OS and quality of life achieved up to now, it is important to consider that the highly selected population of clinical trials doesn’t always accurately predict the clinical impact of therapies in the general population, hence having real world data is an essential tool to guide physicians in daily clinical practice. Methods: In this observational, multicentre, prospective study, we evaluated the safety profile and the incidence of dose reductions, temporary interruptions and treatment discontinuation due to adverse events, in a real–world cohort of Italian pre or postmenopausal HR+/HER2– MBC pts who received a first line combination of ribociclib and letrozole. Results: A total of 78 MBC patients were included in the analysis. The median duration of treatment was 17 (1–61) months. At the time of ribociclib initiation, 13 (16.7%) pts already presented an altered transaminase value whereas liver metastases were present in 17 pts (21.8%). Ten (12.8%) pts experienced hepatic toxicity while on treatment. The median number of cycles for liver toxicity was 3 (1–18). The most common hepatic event was transaminase level increase in 7 (8.8%) pts. Such event occurred more frequently in the group of pts with normal baseline liver function. Hepatic toxicity was grade 1 in 3 (3.8%) pts, grade 2 in 3 (3.8%) pts, grade 3 in 3 (3.8%) pts and grade 4 in 1 (1.3%) pt. Dose reduction due to hepatic toxicity occurred in 3 (3.8%) pts, in particular one of them needed dose reduction from 600 mg to 400 mg, one from 600 mg to 200 mg whereas treatment discontinuation was applied in the last patient. Median time of treatment interruption due to hepatotoxicity was 29 (14–45) days and 3 (3.8 %) pts discontinued ribociclib due to adverse events. No deaths due to liver failure have been reported. Conclusions: Hermione–8 trial support a manageable safety profile of the combination ribociclib and letrozole in MBC patients treated in a real–world clinical setting, confirming toxicity profile in line with the results presented in the MONALEESA clinical trials. Dose reductions, temporary interruptions and discontinuation of treatment due to adverse events have been limited and seems comparable to the results from MONALEESA trials. [Table: see text]