Postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX to improve outcomes of patients with hepatocellular carcinoma with microvascular invasion: A prospective multicenter, phase 3, randomized, controlled clinical trial.

4013 Background: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX (5- fluorouracil, leucovorin, and oxaliplatin) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). Methods: In this randomized, open label, multicenter, phase 3 trial, histologically confirmed HCC patients with MVI were randomized (1:1) to receive either 1 to 2 cycles of adjuvant HAIC-FOLFOX (treatment group) or routine follow-up without any adjuvant treatment (control group). The primary endpoint was disease free survival (DFS), Secondary endpoints included overall survival (OS), recurrence rate and safety. Survival rates were calculated by the Kaplan-Meier plots. Adverse events (AE) were graded according to NCI-CTCAE version 5.0. Results: Between June, 2016 and August, 2021, a total of 315 patients in 5 centers were enrolled in to the study and eligible patients were randomly assigned to the treatment group (n = 157) or control group (n = 158) and were included in the intention-to-treat (ITT) population. Among these 14 patients from treatment group and 15 patients from control group were excluded from the per-protocol (PP) population. 148 patients in treatment group underwent at least 1 cycle of HAIC were included in safety analyses. The median DFS of treatment group and control group were 27.0 months (95% CI, 17.0-37.0) and 11.3 months (95% CI, 7.9-14.7), respectively in ITT population, while which was 20.4 months (95% CI, 9.5-31.3) and 9.7 months (95% CI, 6.9-12.4), respectively in PP population. The DFS were significantly better in the treatment group than in the control group in both ITT population and PP population (p = 0.001 and < 0.001, respectively). The DFS rates at 1, 2, and 3-years were 64.3%, 50.4%, and 44.3% in treatment group and 47.3%, 33.3%, and 24.2% in control group, respectively in ITT population, while which were 64.0%, 48.2%, and 42.2% in treatment group and 43.3%, 27.1%, and 18.4% in control group, respectively in PP population. The OS rates at 1, 2, and 3-year for the treatment group were 94.7%, 87.6%, and 80.5%, and were 91.9%, 85.9%, and 77.0% for the control group, respectively in ITT population, while which were 94.9%, 86.7%, and 80.9% in treatment group and 91.8%, 84.9%, and 75.3% in control group, respectively in PP population. Furthermore, in ITT population, there were 63 (40.1%) patients in the treatment group and 88 (55.7%) patients in the control group had recurrence. Majority of the AEs observed were grade 0-1 (n = 124 (83.8%)) and no treatment related death was observed during the study period. Conclusions: Postoperative adjuvant HAIC with FOLFOX significantly improved the survival benefits with acceptable toxicities in HCC patients with MVI. Clinical trial information: NCT03192618.