Response to systemic treatments in advanced fibrolamellar carcinoma: A French multicenter retrospective cohort of the AGEO

e16194 Background: Fibrolamellar carcinomas (FLC) are rare hepatic malignancies affecting young patients without chronic liver disease, often diagnosed at an advanced stage. Few data are available regarding efficacy of systemic anti-tumor treatments. Main objective was to explore response according to RECIST 1.1 criteria in the first line setting in advanced FLC patients. Methods: This retrospective multicentric French cohort included 44 patients with advanced FLC who received at least one systemic treatment and had one morphological evaluation, performed every 2-3 months. Results: Median age at diagnosis was 24 years (range 13-62), 59.1% were female, 38% were at stage IVa (lymph node involvement) and 42% at stage IVb (metastatic involvement). Responses were analyzed in 42 patients, 7 receiving neoadjuvant treatment and 35 patients receiving a first line palliative treatment. There was no complete response, 14.3% (n = 5) had a partial response (PR), 37.1% (n = 13) had stable disease (SD) and 48.6% (n = 17) had progressive disease. GEMOX was the most prescribed regimen (n = 8) with a disease control rate (PR+SD) at 25% (PR = 12.5% and SD = 12.5%). Doxorubicine-platine was the second most prescribed association (n = 5) with a disease control rate at 80% (PR = 40% and SD = 40%). Tyrosine kinase inhibitors, i.e. sorafenib (n = 10) and sunitinib (n = 3) showed no response and a rate of SD of 40% and 33% respectively. The association of doxorubicine-platine plus sorafenib was used in 4 patients, with one PR and three SD. Only one patient received immunotherapy (nivolumab and ipilimumab), but progressed at first evaluation at two months. Median overall survival was 3.3 years. Five years overall survival was 35% (95%CI = 0.23-0.54). Patients who underwent surgery had a better prognosis (55 months vs 15.5 months). Unfortunately, disease relapsed quickly after surgery, with a median relapse-free survival of 11 months. Conclusions: Advanced fibrolamellar carcinomas have a low chemosensitivity to either cytotoxic chemotherapy or tyrosine kinase inhibitors. Larger studies are warranted to define a standard of care for these rare tumors requiring treatment in an expert centre, either with a molecular screening.