NeoTACE: A multicenter, randomized study evaluating the efficacy and safety of neoadjuvant HAIC for TACE plus donafenib in BCLC B stage hepatocellular carcinoma outside of up-to-seven

TPS4186 Background: Transarterial chemoembolization (TACE) is standard treatment for hepatocellular carcinoma (HCC) patients in BCLC B stage, while a number of studies demonstrated compromised effect of TACE for patients with large HCC or tumor burden outside of up-to-7. Recently, two phase 3 studies showed the survival benefit of Hepatic arterial infusion chemotherapy (HAIC) for large HCC and as neoadjuvant treatment for HCC outside of Milan criteria. A Phase 3 study also showed the survival benefit of donafenib for unresectable HCC compared with sorafenib. Here, we propose a prospective randomized study to investigate the benefit of HAIC as a neoadjuvant therapy for TACE plus donafenib in unresectable BCLC B stage HCC outside of up-to seven. Methods: This is a multicenter, open-label, randomized study designed to evaluate the efficacy and safety of neoadjuvant HAIC for TACE plus donafenib compared with TACE plus donafenib in BCLC B stage unresectable HCC outside of up-to-seven. Participants are randomized in 1:1 ratio to either Arm A, receiving 2-4 cycles neoadjuvant HAIC treatment plus donafenib initially, then TACE plus donafenib sequentially, or Arm B, just receiving TACE treatment plus donafenib. HAIC consisted of infusions of oxaliplatin (35 mg/m2 for 2 hours), followed by 5-fluorouracil (600 mg/m2 for 22 hours) on day1-3 every 4 weeks. The primary endpoint is PFS, and the secondary endpoints are OS, ORR, DCR, and adverse events. We hypothesize that neoadjuvant HAIC for TACE plus donafenib will improve PFS from 6 months to 11 months, with the hazard ratio of 0.55. With one-sided significance level of 0.05 and power of 0.8, the sample size for randomization will be 156. The study, registered with clinical trial ID of NCT05171166, started enrolment in Feb 2022. As of Oct 2022, 65 patients have been enrolled and 11 patients have been randomized. Clinical trial information: NCT05171166 .