| Background & AimPrimary liver cancer is one of the most common malignant tumors in clinical practice.Hepatocellular carcinoma(HCC)accounts for a large proportion of primary liver cancer.HCC is the fourth most common cause of cancer-related deaths worldwide and the third most common cause of cancer deaths in China.Overall,the outcomes for HCC patients are poor,because diagnosis often occurs in patients with advanced-stage.Hepatocellular carcinoma presents one of the most important therapeutic challenges in oncology.Sorafenib is the only recommended treatment recommended by American Association for the Study of Liver Diseases(AASLD)based on the reported survival advantage from randomized trials against placebo.The modest overall survival benefits of sorafenib(approximately 2.5 months)and high price raise questions about whether its use as only therapy is appropriate.The Chinese herbal formula Jie-du granule preparation(JD),which is widely used for treating HCC,comprises anticancer and detoxifying endotoxic Chinese herbal medicines prepared according to the theory of traditional Chinese herbal medicine.In the present study,we aimed to assess the efficacy,safety and cost-effectiveness of Jiedu Granule and Sorafenib in the treatment of advanced HCC.MethodsWe conducted a prospective analysis of the data of consecutive patients with advanced HCC who received either sorafennib or Jiedu Granule at the Changhai Hospital and Eastern Hepatic Surgery Hospital between Nov 2013 and Dec 2016.The study protocl was approved by the Institutional Ethics Review Board.The patients was followed up until the data of death or when censored at the latest data.The primary endpoint is overall survival.The secondary endpoints were progression-free survival and safety.Patients' survival and progression times were analyzed by the Kaplan-Meier method and Log-rank test.We performed univariate and multivariate analyses to identify predictors of survival.A Markov model comprising three health states(progression-free survival,progressive disease,and death)was created to simulate the process of advanced HCC.We calculated the data on cost from the perspective of Chinese patients.Incremental cost effectiveness ratios(ICERs)were calculated for sorafenib-treated and control patients.Sensitivity analyses were also performed to explore the impact of several essential variables on the results of the analysis.We performed univariate and multivariate analyses to identify predictors of survival.ResultsOne hundred and sixty two sorafenib(52.8±10.1 years,male 90.7%)and 185 Jiedu Granule patients(55.9±11.2 years,male 85.4%)were prospectively collected based on the following criteria: BCLC-C stage,Child-Pugh class A/B,performance status ?2,and no previous systemic chemotherapy.The median follow-up duration was 18.53 months(range 2-40 months).Median overall survival was 6.7 months(95%CI:5.33-10.40)in patients treated with Jiedu Granule,compared with 8 months(95%CI:7.27-10.53)in those who received sorafenib(P=0.402).Median PFS was 3.22 months(95%CI:2.97-3.70)in the Jiedu Granule group compared with 3.57 months(95%CI:2.77-4.03)in the sorafenib group(P=0.442).There was no significant difference between the two groups in the median time.We have identified ECOG performance status,largest tumor size,alpha fetoprotein,ALT and AST were significantly associated with poor overall survival in advanced HCC patients.ECOG performance status,alpha fetoprotein,AST were significantly associated with poor PFS in advanced HCC patients.Diarrhea,hand-foot skin reaction were more frequent in the sorafenib group.In the propensity score-matched cohort(155 pairs),median overall survival was 6.7 months(95%CI:5.33-10.40)in patients treated with Jiedu Granule,compared with 8 months(95%CI:7.27-10.53)in those who received sorafenib(P=0.402).Median PFS was 3.22 months(95%CI:2.97-3.70)in the Jiedu Granule group compared with 3.57 months(95%CI:2.77-4.03)in the sorafenib group(P=0.442).There was no significant difference between the two groups in the median time.We have identified ECOG performance status,largest tumor size,alpha fetoprotein,ALT and AST were significantly associated with poor overall survival in advanced HCC patients.ECOG performance status,alpha fetoprotein,AST were significantly associated with poor PFS in advanced HCC patients.The results of propensity score-matched cohort are consistent with the outcomes of previous study.According to the pharmaco-economic implications of Jiedu Granule or sorafenib for advanced hepatocellular carcinoma,treatment with Jiedu Granule provided an effectiveness gain of 0.34 quality-adjusted life year at an average cost of ?32122.584,whereas sorafenib brought 0.42 quality-adjustedlife year at a cost of ?266864.155.The incremental cost effectiveness ratio(ICER)for sorafenib compared to Jiedu Granule was ?635390.845 per quality-adjusted life year gained(cost/QALY),which was higher than the willingness to pay threshold of China according to World Health Organization's guideline.One-way sensitivity analysis revealed that the cost of progression free survival for sorafenib treatment,utility of progression free survival for sorafenib and Jiedu Granule,cost of progression free survival for Jiedu Granule were the most sensitive parameters in all cost scenarios.ConclusionsIn conclusion,Jiedu Granule preparation provides similar efficacy to sorafenib in this setting,and is more safety,more cost-effective. |
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