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.
Study Details
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.
Overall Survival
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).
KEY POINTS
- FOLFOX-HAIC significantly improved overall survival and progression-free survival vs TACE.
- Median overall survival was 23.1 vs 16.1 months.
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).
Adverse Events
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.
