TACE with idarubicin-eluting beads compared with TACE with epirubicin-eluting beads in BCLC B-stage HCC: Interim results of a randomized, double-blind, parallel-controlled, phrase IV multicenter study.

Abstract

4068 Background: The lack of effectiveness of a cytotoxic agent for intra-arterial use in HCC has been a major limitation for improved outcomes. Idarubicin, an anthracycline-based drug, is currently used as the first-line treatment option for acute myeloid leukaemia. Incredibly, a previous study showed that idarubicin has better anti-tumor effects on HCC compared with oxaliplatin and 5-fluorouracil in vitro, and two single-arm studies of idarubicin lipiodol TACE reported good therapeutic outcomes and acceptable adverse drug reactions. Methods: This randomized, double-blind, parallel controlled, phrase IV, multicenter trial was conducted from July 2020. Patients with BCLC stage B HCC were randomly assigned in a 1:1 ratio to receive TACE loaded with 10 mg idarubicin (IT group) or 40 mg epirubicin (ET group). The sample size of 120 was needed in each group according to calculation. The primary endpoint was progression-free survival (PFS, defined as the time from randomization until progression or death from any cause). The secondary endpoints were overall survival (OS, defined as the date of randomization to death from any cause), objective response rate (ORR, the proportion of patients with complete response or partial response according to mRECIST), and adverse events. A single interim analysis was planned when appropriately 1/3 (33.3%) of the required 240 patients. To control the type I error rate at the interim analysis, superiority boundaries that were based on Pocock spending function 24 were a P value of less than 0.022 for PFS. The deadline for interim analysis of data is October 1, 2021. Results: Overall, 103 patients (mean age: 56.6 years±11.4; 12 women and 91 men) were randomly assigned to receive either TACE with Idarubicin-eluting beads (n = 50) or TACE with Epirubicin-eluting beads (n = 53). The PFS and OS were not mature on October 1, 2021. The median PFS was significantly longer in the IT group than in the ET group (HR [hazard ratio] = 0.32, P < 0.001). PFS rates were 82.4% and 43.9% at 6 months, and 53.7% and 18.9% at 12 months in IT and ET groups, respectively. The median OS was longer but not significant in the IT group than in the ET group (HR = 0.52, P = 0.058). OS rates were 90.2% and 76.5% at 6 months, and 61.6% and 47.3% at 12 months in IT and ET groups, respectively. TACE with Idarubicin-eluting beads did not improve ORR compared to TACE with Epirubicin-eluting beads according to mRECIST (80.0% vs. 62.3%, P = 0.048). The incidence of myelosuppression was higher in the ET group than in the IT group (22.6% vs. 6.0%, P = 0.024). No difference was observed in other treatment related adverse events. Conclusions: This study proved that Idarubicin could be a good safety profile and superior PFS and ORR than Epirubicin when used as part of a TACE regimen for BCLC B stage HCC. Longer follow-up is needed to confirm this conclusion. Clinical trial information: ChiCTR2000034758.