In a Chinese phase III trial reported in the Journal of Clinical Oncology, Li et al found that hepatic arterial infusion chemotherapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin; FOLFOX-HAIC) improved overall survival vs transarterial chemoembolization (TACE) as first-line treatment for large unresectable hepatocellular carcinoma.
In the open-label multicenter trial, 315 patients with unresectable disease (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned between October 2016 and November 2018 to receive FOLFOX-HAIC (n = 159) or TACE (n = 156). FOLFOX-HAIC consisted of oxaliplatin at 130 mg/m2, leucovorin at 400 mg/m2, fluorouracil bolus at 400 mg/m2 on day 1, and fluorouracil infusion at 2,400 mg/m2 for 24 hours once every 3 weeks for up to six cycles. TACE consisted of epirubicin at 50 mg, lobaplatin at 50 mg, and lipiodol and polyvinyl alcohol particles every 6 weeks.
The primary endpoint was overall survival in intention-to-treat analysis. Follow-up ended in November 2020.
Median overall survival was 23.1 months (95% confidence interval [CI] = 18.5–27.7 months) in the FOLFOX-HAIC group vs 16.1 months (95% CI = 14.3–17.9 months) in the TACE group (hazard ratio [HR] = 0.58, 95% CI = 0.45–0.75, P < .001). The benefit remained significant in analysis adjusting for tumor size (HR = 0.57, 95% CI = 0.44–0.74, P < .001).
Median progression-free survival was 9.6 months (95% CI = 7.4–11.9 months) in the FOLFOX-HAIC group vs 5.4 months (95% CI = 3.8–7.0 months) in the TACE group (HR = 0.57, 95% CI = 0.45–0.72, P < .001). Median symptomatic progression-free survival was 17.9 months (95% CI = 13.0–22.9 months) vs 10.4 months (95% CI = 8.9–12.0 months; HR = 0.53, 95% CI = 0.41–0.67, P < .001).
Objective response was observed in 73 (46%) vs 28 (18%) patients (P < .001), with complete response in 20 (13%) vs 5 (3%) patients (P = .002). Disease control rates were 82% vs 61% (P < .001).
The TACE group had higher rates of treatment-related grade 3 or 4 elevated alanine aminotransferase (8% vs 19%, P = .005), elevated aspartate aminotransferase (18% vs 28%, P = .03), and hyperbilirubinemia (1% vs 6%, P = .01). Serious adverse events occurred in 19% of the FOLFOX-HAIC group vs 30% of the TACE group (P = .03). Adverse events led to death in two patients in each group.
The investigators concluded, “FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.”
Ming Shi, MD, of the Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Key R&D Program of China, National Natural Science Foundation of China, National Science and Technology Major Project of China, and others. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.