Background & Aims
No adjuvant therapy has been shown to extend survival of patients with hepatocellular carcinoma (HCC) receiving curative treatment. We investigated whether injections of activated cytokine-induced killer (CIK) cells (CD3+/CD56+ and CD3+/CD56- T cells and CD3-/CD56+ natural killer cells) prolongs recurrence-free survival of patients following curative therapy for HCC.
We performed a multi-center, randomized, open-label, phase 3 trial of the efficacy and safety of adjuvant immunotherapy with activated CIK cells (created by incubation of patients’ peripheral blood mononuclear cells with interleukin-2 and an antibody against CD3). The study included 230 patients with HCC treated by surgical resection, radiofrequency ablation, or percutaneous ethanol injection at university-affiliated hospitals in Korea. Patients were randomly assigned to receive immunotherapy (injection of 6.4 ×109 autologous CIK cells, 16 times during 60 weeks) or no adjuvant therapy (controls). The primary endpoint was recurrence-free survival; secondary endpoints included overall survival, cancer-specific survival, and safety.
The median time of recurrence-free survival was 44.0 months in the immunotherapy group and 30.0 months in the control group (hazard ratio [HR] with immunotherapy, 0.63; 95% confidence interval [CI], 0.43-0.94; P=.010 by one-sided log-rank test). HRs were also lower in the immunotherapy than control group for all-cause death (0.21; 95% CI, 0.06-0.75; P=.008) and cancer-related death (0.19; 95% CI, 0.04-0.87; P=.02). A significantly higher proportion of patients in the immunotherapy group than the control group had an adverse event (62% vs 41%, P=.002), but the proportion of patients with serious adverse events did not differ significantly between groups (7.8% vs 3.5%, P=.15).
In patients who underwent curative treatment for HCC, adjuvant immunotherapy with activated CIK cells increased recurrence-free and overall survival. ClinicalTrials.gov number: NCT00699816.
Keywords : liver cancer; clinical trial; IL2; NK cell