Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study

Abstract

PURPOSE To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions

“…Adjuvant HAIC with FOLFOX significantly improved RFS with acceptable toxicity in HCC patients with MVI. 55 However, these findings need to be confirmed by further trials.…”

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Chinese perspective

“…Moreover, the strong antitumor efficacy for intrahepatic lesions enabled FOLFOX-HAIC as a conversion therapy to transform unresectable HCC to resectable one [63]. And a recent study reported that 1-2 cycles of FOLFOX-HAIC in the adjuvant setting significantly improved recurrence free survival (RFS) for patients with microvascular invasion [64].…”

Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis

“…Adjuvant therapy may provide survival bene ts for HCC patients with MVI(19). A recent clinical trial showed that adjuvant HAIC with FOLFOX largely improved the disease-free survival bene ts in HCC patients with MVI(20). Our study provided a comprehensive landscape of HCCs with MVI, which might give new clues for exploring novel immunotherapies for HCC patients with MVI.MVI is likely to progress into IM, Wang et al reported that IM patients had worse prognoses compared with MO patients after liver transplantation(21).…”