Lenalidomide for advanced hepatocellular cancer (HCC) in patients progressing on or intolerant to sorafenib.

Abstract

4159 Background: Lenalidomide inhibits fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). FGF has recently been reported to be an important growth factor in HCC. There is currently no standard of care for patients who progress after sorafenib. Therefore, we performed a phase II study to determine the activity of lenalidomide in second-line HCC. Methods: Patients with advanced HCC who progressed or were intolerant to sorafenib were eligible. Prior chemoembolization, RFA or surgery was allowed. Eligibility criteria also included bilirubin ≤ 4 mg/dL, AST and ALT ≤ 5 times upper limit of normal, ECOG performance status 0-2, platelet count ≥ 60,000/mm3, absolute neutrophil count > 1,000/mm3, and creatinine < 2 mg/dL. Patients were treated with lenalidomide 25 mg orally days 1-21 of a 28 day cycle until disease progression or unacceptable toxicities. A preplanned interim analysis was included to evaluate biologic activity after 13 patients enrolled. To continue the study, biologic activity defined as a partial response by RECIST criteria or > 50% decline in AFP was required in 2 of 13 patients. Results: Preplanned interim analysis was undertaken when study enrollment reached 13 out of the total planned 40 patients. Of the first 13 patients, the median age was 66 years (44-86 years). Eight patients were Child-Pugh A, 3 patients were B and 2 patients were C. Nine patients had extrahepatic disease. Five of 13 patients (38%) had a > 50% reduction in AFP including one patient with a reduction in AFP from 56,900 to 5 ng/mL. Three patients had radiographic partial responses. One patient had grade 4 neutropenia. Grade 3 non-heme toxicities include fatigue (n = 2), diarrhea (n = 2), liver dysfunction (n = 1). Conclusions: Lenalidomide is well tolerated in patients with advanced HCC and significant hepatic dysfunction. Promising, and in some patients dramatic, activity was demonstrated. The study's preplanned criteria for preliminary activity was met and the study will continue to accrue to 40 patients. Investigations are needed to explore the mechanism of action of lenalidomide in HCC. Supported in part by Celgene. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Genentech, Roche, sanofi-aventis