In a Chinese phase III trial (FOHAIC-1) reported in the Journal of Clinical Oncology, Lyu et al found that hepatic arterial infusion chemotherapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin; HAIC-FO) significantly prolonged overall survival vs sorafenib in patients with advanced hepatocellular carcinoma who had received no prior systemic therapy.
Study Details
In the trial, 262 patients were randomly assigned between May 2017 and May 2020 to receive HAIC-FO (n = 130) or sorafenib at 400 mg twice daily (n = 132). HAIC-FO consisted of oxaliplatin at 130 mg/m2, leucovorin at 200 mg/m2, fluorouracil at 400 mg/m2, and fluorouracil at 2,400 mg/m2 sequentially infused via catheter once every 3 weeks.
The primary endpoint was overall survival in the intention-to-treat population.
Key Findings
Among all patients, median tumor size was 11.2 cm (interquartile range [IQR] = 8.5–13.7 cm), macrovascular invasion was present in 65.6%, and 49.2% had > 50% tumor volume involvement of the liver or Vp-4 portal vein tumor thrombosis.
Median follow-up was 17.1 months (IQR = 11.2–37.6 months) in the HAIC-FO group and 19.8 months (IQR = 12.3–21.4 months) in the sorafenib group.
HAIC-FO achieved better survival outcomes than sorafenib in advanced hepatocellular carcinoma, even in association with a high intrahepatic disease burden.— Lyu et al
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At data cutoff (October 2020), median overall survival was 13.9 months (95% confidence interval [CI] = 10.6–17.2 months) in the HAIC-FO group vs 8.2 months (95% CI = 7.5–9.0 months) in the sorafenib group (hazard ratio [HR] = 0.408, 95% CI = 0.301–0.552, P < .001).
In the high-risk population of patients with > 50% tumor volume involvement of the liver or Vp-4 portal vein tumor thrombosis, median overall survival was 10.8 months vs 5.7 months (HR = 0.343, 95% CI = 0.219–0.538, P < .001).
Median progression-free survival was 7.8 months (95% CI = 6.0–9.6 months) in the HAIC-FO group vs 4.3 months (95% CI = 3.6–5.0 months) in the sorafenib group (HR = 0.451, 95% CI = 0.340–0.598, P < .001).
Objective response was observed in 31.5% vs 1.5% of patients (P < .001). Median overall survival among HAIC-FO responders vs nonresponders was 19.3 vs 10.6 months (HR = 0.323, 95% CI = 0.186–0.560, P = .002).
In the HAIC-FO group, tumor downstaging occurred in 16 patients (12.3%); of these, 15 received curative surgery or ablation and exhibited a median overall survival of 20.8 months, with a 1-year rate of 93.8%.
The investigators developed a 15-gene prediction model that identified 83% of patients with response to HAIC-FO.
Treatment-related grade 3 or 4 adverse events occurred in 20.3% of patients in the HAIC-FO group vs 48.1% of the sorafenib group.
The investigators concluded, “HAIC-FO achieved better survival outcomes than sorafenib in advanced hepatocellular carcinoma, even in association with a high intrahepatic disease burden.”
Ming Zhao, MD, of the Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Natural Science Foundation of China. For full disclosures of the study authors, visit ascopubs.org.
