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

Background Lenalidomide has immunomodulatory and anti‐angiogenic effects and showed moderate anti‐tumour efficacy in patients with. advanced hepatocellular carcinoma ( HCC ) Aim To explore potential biomarkers of lenalidomide efficacy as second‐line therapy for HCC . Methods Eligible patients were diagnosed with advanced HCC , documented progression on sorafenib, and Child‐Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1‐21 every 4 weeks. The primary endpoint was 6 month progression‐free survival rate. Early α ‐fetoprotein response was defined as a > 20% decline of α ‐fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast‐enhanced magnetic resonance imaging, was defined as a > 40% decline in K trans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed. Results Fifty‐five patients were enrolled. The response rate was 13%, and the disease‐control rate was 53%. The 6 month progression‐free survival rate was 9.1%. The median progression‐free and overall survival was 1.8 months and 8.9 months respectively. Early α ‐fetoprotein response was significantly associated with higher disease‐control rate (76% vs 22%, P = .001) and longer progression‐free survival ( P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre‐treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression‐free survival ( P < .001) and overall survival ( P = .042). Conclusions Lenalidomide exhibited moderate activity as second‐line therapy for advanced HCC . Its immunomodulatory effects should be further explored ( www.clinicaltrials.gov NCT 01545804).