Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy
Journal
Alimentary Pharmacology and Therapeutics
Journal Volume
46
Journal Issue
8
Date Issued
2017-10-01
Author(s)
Abstract
© 2017 John Wiley & Sons Ltd 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 Ktrans 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 NCT01545804).
SDGs
Other Subjects
alpha fetoprotein; lenalidomide; sorafenib; tumor marker; alpha fetoprotein; angiogenesis inhibitor; antineoplastic agent; carbanilamide derivative; lenalidomide; nicotinamide; sorafenib; thalidomide; tumor marker; adult; advanced cancer; aged; antiangiogenic activity; antineoplastic activity; Article; cancer control; cancer growth; Child Pugh score; controlled study; drug dose reduction; drug efficacy; drug response; drug safety; drug withdrawal; dynamic contrast-enhanced magnetic resonance imaging; female; human; hyperbilirubinemia; hypertransaminasemia; immunomodulation; infection; liver cell carcinoma; major clinical study; male; neutropenia; peripheral lymphocyte; phase 2 clinical trial; priority journal; progression free survival; pruritus; rash; analogs and derivatives; clinical trial; disease exacerbation; disease free survival; liver cell carcinoma; liver tumor; metabolism; middle aged; treatment outcome; Adult; Aged; alpha-Fetoproteins; Angiogenesis Inhibitors; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Hepatocellular; Disease Progression; Disease-Free Survival; Female; Humans; Liver Neoplasms; Male; Middle Aged; Niacinamide; Phenylurea Compounds; Thalidomide; Treatment Outcome
Type
journal article