Exploring the efficacy of GEMOX-lenvatinib after GEMOX ± sorafenib failure in unresectable fibrolamellar carcinoma.

e16267 Background: Fibrolamellar Carcinoma (FLC) is a rare, aggressive primary liver cancer affecting children and young adults. It is often diagnosed at an advanced stage with minimal or nonspecific symptoms, making early detection challenging. Surgical resection with negative margins (R0) remains the only curative treatment. However, approximately one-third of patients present with unresectable tumors and are thus considered incurable, with poor survival outcomes. There is a pressing need for therapies to convert unresectable FLC to resectable tumors. Gemcitabine and oxaliplatin (GEMOX), with or without sorafenib (SOR), are commonly used, though success rates remain low. Recently, GEMOX combined with lenvatinib (GEMOX-LEN) has shown promise in converting unresectable FLC to resectable tumors. However, its efficacy after prior GEMOX or GEMOX-SOR remains uncertain. Methods: In this study, we compare the efficacy of GEMOX-LEN following GEMOX ± SOR in patients with unresectable FLC. We report on 21 stage IV unresectable FLC patients (13 male, 8 female, median age 20.43 years) from the xCures database who previously received GEMOX ± SOR, followed by GEMOX-LEN. A median of 4 prior cycles of therapy were given. 15 patients had failed GEMOX alone, while 6 failed GEMOX-SOR, with all 6 also having received PLADO in a clinical trial. All patients received GEM (1000 mg/m²) and OX (100 mg/m²) intravenously every two weeks, with daily oral LEN (8 mg) or SOR (200-400 mg). Treatment responses were evaluated using RECIST 1.1 criteria. Results: Of the 21 patients treated with GEMOX-LEN, 11 became surgical candidates, 8 did not become surgical candidates, and 2 are still undergoing treatment. Resection outcomes were classified as R0 = 8, R1 = 0, and R2 = 3. Treatment response included 1 Complete Response, 9 Partial Responses, 11 Stable Disease, and none with Progressive Disease. The median RECIST 1.1 responses for GEMOX-LEN was -15%, compared to +6% for GEMOX alone and + 11% for GEMOX-SOR. The median volume reduction for GEMOX-LEN was -65% %, compared to +30% for GEMOX alone and + 17% for GEMOX-SOR. The median reduction in circulating tumor DNA (ctDNA) was -100%. Conclusions: This study supports the hypothesis that GEMOX-LEN may help convert unresectable FLC to respectable tumors even after prior therapy failure. Prospective trials are needed to confirm these findings. GEMOX cohort comparison. Cohort n Median number of cycles Surgical candidates Median volume response TTP month cTDNA GEMOX 6 2.6 0 +17% 6.0 ND GEMOX-SOR 15 4,0 0 +30% 3.7 ND GEMOX-LEN 21 11 9 -65% 13 -100%