Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion

Abstract

IMPORTANCE Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study.OBJECTIVE To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion. DESIGN, SETTING, AND PARTICIPANTSThis randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months.INTERVENTIONS Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , fluorouracil bolus 400 mg/m 2 on day 1, and fluorouracil infusion 2400 mg/m 2 for 46 hours, every 3 weeks). MAIN OUTCOMES AND MEASURESThe primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment.RESULTS For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]).CONCLUSIONS AND RELEVANCE Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS–ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO

“…Asian dug approvals and reimbursements for HCC according to country, and ESMO-Magnitude of Clinical Benefit Score (MCBS) 125 Drugs been supported by a Chinese study showing the superiority of hepatic arterial infusion of FOLFOX plus sorafenib versus sorafenib alone in patients with advanced HCC. 98 Thus, HAIC either alone or in combination with sorafenib may be an option for certain selected patients with advanced HCC. Finally, several randomised phase III clinical trials have been conducted to investigate the potential of other targeted agents in the first-line treatment of HCC compared with sorafenib.…”

Treatment of hepatocellular carcinoma during the COVID‐19 outbreak: The Working Group report of JAMTT‐HCC

“…• Select patients likely to benefit, including those refractory to systemic therapy with advanced vascular invasion 31,[43][44][45] Alternative therapy: systemic therapy ALBI, albumin-bilirubin; EASL, European Association for the Study of the Liver; HAIC, hepatic arterial infusion chemotherapy; HCC, hepatocellular carcinoma; ILCA, International Liver Cancer Association; PS, performance status; RFA, radiofrequency ablation; TACE, transarterial chemoembolization.…”

Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

“…The mOS of the patients treated with HAIC and sorafenib was 315 days, which was significantly longer than that treated with HAIC alone (197days) [30]. A prospective randomized controlled trial recruited 247 HCC patients with PVTT showed that HAIC combined with sorafenib could significantly prolong the survival time (mOS: 13.37 vs. 7.13 months, respectively), and the progression-free survival time (median: 7.03 vs 2.6 months, respectively) of patients compared with sorafenib alone [31]. The mOS of patients in combination therapy group and sorafenib monotherapy group was 18.17 and 10.87 months, respectively in type I -II PVTT subgroup, 13.47 and 6.27 months respectively in type III PVTT subgroup, 9.47 and 5.5 months respectively in type IV PVTT subgroup [31].…”