Lenalidomide for second-line treatment of advanced hepatocellular cancer (HCC): A Brown University Oncology Group phase II study.

Abstract

4098 Background: Lenalidomide inhibits fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and multiple tumor growth pathways. There is 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 therapy. Methods: Patients with advanced HCC who progressed on or were intolerant to sorafenib were eligible. Prior chemoembolization, RFA, or surgery were 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 >1000/mm3, and creatinine <2mg/dL. Patients were treated with lenalidomide 25mg orally days 1-21 of a 28 day cycle until disease progression or unacceptable toxicities. The planned original sample size was 25 patients but when early activity was demonstrated the study was expanded to 40 patients. Results: The study has completed accrual of 40 patients. The median age was 60.5 years (17-88 years). Nineteen patients were Child-Pugh A, 16 patients were B, and 5 patients were C. Twenty four patients had extrahepatic disease. Preliminary data is available on the first 37 patients. One patient had grade 4 neutropenia. Grade 3 toxicities included ANC (n=2), fatigue (n=4), rash (n=2), arthritis (n=1), diarrhea (n=1), dehydration (n=2). One patient developed variceal bleeding which precipitated encephalopathy and death. Of the 32 patients with elevated baseline AFP, nine (28%) had a >50% reduction including one patient with a reduction in AFP from 56,900ng/ml to 5 ng/ml. Six of the first 37 patients (16%) had a radiographic partial response. Two patients achieved a complete response and have not progressed at 36 and 32 months. Conclusions: Lenalidomide can be administered to patients with advanced HCC and significant hepatic dysfunction. Promising, and in a small percentage of patients, dramatic and durable activity has been demonstrated. Investigations are underway to explore the mechanism of action of lenalidomide in HCC.