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

• Published in: Alimentary pharmacology & therapeutics Vol. 46; no. 8; pp. 722 - 730
• Main Authors: Shao, Y.‐Y., Chen, B.‐B., Ou, D.‐L., Lin, Z.‐Z., Hsu, C.‐H., Wang, M.‐J., Cheng, A.‐L., Hsu, C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-10-2017
• Subjects: Adult; Aged; alpha-Fetoproteins - metabolism; Angiogenesis; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Biomarkers; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - drug therapy; Disease control; Disease Progression; Disease-Free Survival; Female; Hepatocellular carcinoma; Humans; Immunomodulation; Immunotherapy; Liver; Liver cancer; Liver Neoplasms - drug therapy; Lymphocytes B; Magnetic resonance imaging; Male; Middle Aged; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Peripheral blood; Phenylurea Compounds - administration & dosage; Survival; Targeted cancer therapy; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Treatment Outcome; Tumors
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.14270

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).