Lenalidomide, which has both immunomodulatory and anti-angiogenic effects, has shown efficacy as second-line treatment for advanced HCC in a Western population. We sought to confirm the findings in an Asian population and explore potential biomarkers.
Eligible patients had histological or clinical diagnosis of HCC, documented progression with or intolerance to sorafenib or other anti-angiogenic therapy, ECOG score 0 or 1, and Child class A. Patients received 25mg/day lenalidomide on days 1-21 every 4 weeks. Tumor response was assessed by RECIST1.1 after 4 and 8 weeks of treatment and every 8 weeks thereafter. The primary endpoint was 6-month progression-free survival (PFS) rate. Early α-fetoprotein (AFP) response was defined as a > 20% decline of AFP levels from baseline within the first 4 weeks of treatment. Vascular response (VR), evaluated using dynamic contrast enhanced-magnetic resonance imaging, was defined as a >40% decline in Ktrans after 2 weeks of treatment.
Fifty-five patients (M/F: 45/10, median age 59.8 years) were enrolled. Underlying liver diseases included hepatitis B (93%), hepatitis C (18%), and alcoholism (11%). All patients had documented progression after sorafenib treatment. The response rate (RR) was 13% (0 complete and 7 partial responses; 22 durable [≥ 8 weeks] stable disease), and the disease control rate (DCR) was 53%. The 6-month PFS rate was 9.1%. The median PFS and overall survival (OS) was 1.8 and 8.9 months, respectively. Early AFP response (17 of 40 patients, 43%) was borderline significantly associated with higher RR (29% vs. 4%, p = 0.067) and significantly associated with higher DCR (76% vs. 22%, p = 0.001) and longer PFS (median, 5.4 vs. 0.9 months, p = 0.020). However, patients with and without AFP response exhibited similar OS (median, 10.7 vs. 8.0 months, p = 0.307). VR (14 of 44 patients, 32%) was not associated with RR (p = 0.364), DCR (p = 0.752), PFS (p = 0.706), or OS (p = 0.135). The safety profile was comparable with other lenalidomide trials.
Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored.
Clinical trial identification
Legal entity responsible for the study
National Taiwan University Hospital
All authors have declared no conflicts of interest.