OP0002 A randomised, single-centre phase 2 study of ginsenoside Rg3 plus transarterial chemoembolisation (TACE) versus TACE alone in Chinese patients with advanced hepatocellular carcinoma

Abstract

Background Ginsenoside Rg3 is a low toxic inhibitor of vascular endothelial growth factor (VEGF), which is implicated in angiogenesis in hepatocellular carcinoma (HCC). This single-centre, open-label, randomised, controlled trial evaluated the efficacy and safety of ginsenoside Rg3 plus transarterial chemoembolisation (TACE) in patients with advanced HCC. Methods Advanced HCC patients (Child-Pugh A) who had no prior systemic therapy were randomly assigned (2:1 ratio) to receive 20 mg twice daily orally (n = 152) combined with TACE or TACE alone (n = 76). The primary endpoint was overall survival (OS). Secondary endpoints included time to progression (TTP), time to untreatable progression (TTUP), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, and safety. Results Median overall survival was 13.2 months (95% confidence interval (CI) 11.15–15.26) in the TACE + Rg3 group compared with 10.1 months (95% CI 9.14–11.06) for those receiving TACE alone (hazard ratio (HR) 0.63 [95% CI 0.46–0.85], p = 0.002). Median TTP was 4.3 months (95% CI 3.32–5.28) in the TACE + Rg3 group compared with 3.2 months (95% CI 2.51–3.89) in the TACE group (HR 0.82 [95% CI 0.62–1.08], p = 0.151). Patients in the TACE + Rg3 group had longer median TTUP (8.3 months [95% CI 7.05–9.55]) than in the TACE group (7.3 months [95% CI 6.40–8.20]; HR 0.76 [95% CI 0.57–1.02], p = 0.063). The most frequently reported Rg3-related grade 3–4 adverse events in 152 patients were constipation (two [1.3%]) and hypertension (six [3.9%]). The incidence of ascites was lower in the TACE + Rg3 group than in the TACE group (23.7% versus 48.7%, p = 0.002), as was the incidence of anorexia [12.5% versus 44.7%, p = 0.000], fatigue (9.9% versus 50.0% p = 0.000), anaemia (36.8% versus 51.3%, p = 0.037), leukopenia (46.7% versus 76.3%, p = 0.000), thrombocytopenia (32.9% versus 50.0%, p = 0.012), and hyperbilirubinaemia (17.8% versus 34.2%, p = 0.028). Interpretation In patients with advanced HCC and sufficient liver function, median survival was nearly 3 months longer for patients treated with TACE and ginsenoside Rg3 than for those who received TACE only.