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.

Lenalidomide as second‐line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy

“…In this study, we found that lenalidomide has modest anti‐tumour efficacy as second‐line therapy for patients with advanced HCC, and the safety profile is similar to those previously reported . The response rate and survival found in our study were consistent with those reported in the phase 2 trial conducted in the USA . Early α‐fetoprotein response may serve as a surrogate efficacy marker, as previously reported for various targeted therapies for HCC .…”

“…Both agents are approved for the treatment of multiple myeloma and show anti‐tumour activity in other hematological malignancies. We and other investigators have previously shown the potential efficacy of thalidomide and lenalidomide for the treatment of advanced HCC . In this open‐label phase II clinical trial, we sought to confirm the efficacy and safety of lenalidomide as second‐line therapy for advanced‐stage HCC (BCLC stage C) and searched for potential clinical, molecular and immunological biomarkers to predict treatment efficacy of lenalidomide in HCC.…”

Phase I Study of Lenalidomide and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

“…Lenalidomide was well tolerated, with rare grade 3 toxicities. The PR rate was 15%, including 2 patients with a durable response of 32 and 36 months [16].…”

MicroRNA‑543 suppresses liver cancer growth and induces apoptosis via the JAK2/STAT3 signaling pathway

“…Liver cancer is the most common malignant liver disease in adults (8). Although the success of its therapy is improving continuously, and there are a variety of therapies, including surgical resection, liver transplantation, radiotherapy and chemotherapy, none has significantly extended the mean 5-year survival of patients with liver cancer (9,10). One of the most important reasons for the high mortality and poor prognosis of patients with liver cancer is that the underlying molecular mechanism is poorly understood.…”