Efficacy And Safety Of Treatments In Patients With Advanced Hepatocellular Carcinoma

Objective: 1.Retrospective meta-analysis of the efficacy and safety of first-line treatment regimens for advanced hepatocellular carcinoma: A systematic evaluation of the efficacy and safety of first-line treatment regimens for advanced hepatocellular carcinoma was performed by means of retrospective meta-analysis to provide a basis for the selection of first-line treatment regimens for advanced hepatocellular carcinoma.2.Retrospective meta-analysis of the efficacy and safety of second-line treatment regimens for advanced hepatocellular carcinoma.meta-analysis: To systematically evaluate the efficacy and safety of second-line treatment regimens for advanced hepatocellular carcinoma by means of mesh meta-analysis,and to provide a basis for the selection of second-line treatment regimens for advanced hepatocellular carcinoma.3.The efficacy and safety of tenofovir alafenamide fumarate,tenofovir disoproxil fumarate and entecavir in the treatment of chronic hepatitis B: To systematically evaluate the efficacy and safety of tenofovir alafenamide fumarate,tenofovir disoproxil fumarate and entecavir in the treatment of chronic hepatitis B by means of mesh metaanalysis,and to provide a basis for the selection of treatment options for chronic hepatitis B.Methods:According to the PRISMA guidelines,a systematic search was conducted in databases such as Pub Med,Embase,and the Cochrane Library,and clinical studies were included or excluded based on the PICOS principle.Data were extracted from the included studies using pre-set tables,and Rev Man 5.4 software was used to evaluate the quality of the extracted articles.R software(version 4.2.2)and Stata SE 16 were used to jointly analyze and synthesize the evidence for two topics: 1.the efficacy and safety of immune combination therapy as a first-line treatment for advanced liver cancer,and 2.the effectiveness and safety of second-line treatment for advanced liver cancer,and 3.the efficacy and safety of tenofovir alafenamide fumarate,tenofovir disoproxil fumarate and entecavir in the treatment of chronic hepatitis B.Network meta-analyses were performed for all three topics.Results:1.Network meta-analysis of the efficacy and safety of first-line immune combination therapy for advanced liver cancer patients: 5 RCTs with a total of 3046 patients were included.Meta-analysis results showed that the efficacy of combination therapy was superior to the past monotherapy with sorafenib,except for the atezolizumab + cabozantinib regimen,which was inferior to sorafenib(HR: 0.90,95%CI: 0.69-1.16)in the comparison of the main outcome indicator,overall survival.The efficacy of the other treatment regimens,including the camrelizumab + apatinib regimen(HR: 0.52,95% CI: 0.41-0.66),the sintilimab + IBI305 regimen(HR: 0.56,95% CI: 0.45-0.69),the atezolizumab + bevacizumab regimen(HR: 0.66,95% CI:0.51-0.85),and the durvalumab + tremelimumab regimen(HR: 0.78,95% CI: 0.65-0.93),were superior to sorafenib.The atezolizumab + cabozantinib regimen was better than sorafenib in terms of progression-free survival(HR: 0.63,95% CI: 0.48-0.83),objective response rate(HR: 2.79,95% CI: 1.43-5.44),and disease control rate(HR:2.65,95% CI: 1.83-3.83).Overall,the efficacy of immune combination therapy was better than that of sorafenib monotherapy.Among the comparisons between various immune therapy regimens,except for the poorer efficacy of the durvalumab +tremelimumab combination group than the other groups,the efficacy of the other treatment regimens showed similar effectiveness.In terms of safety,the durvalumab +tremelimumab combination group performed the best,with a lower incidence of treatment-related adverse reactions,diarrhea,and hypertension than other interventions.The safety of the camrelizumab + apatinib combination group was higher than that of other interventions in terms of treatment-related adverse reactions and diarrhea.2.In second-line treatment of patients with advanced hepatocellular carcinoma after the failure of first-line sorafenib therapy,there is little difference in the effectiveness of various second-line treatment options,except for the fact that the effect of pembrolizumab on disease control rate is better than other interventions.Other interventions,including apatinib(OR: 0.31,95%CI: 0.13-0.72),cabozantinib(OR: 0.35,95%CI: 0.16-0.76),and regorafenib(OR: 0.37,95%CI: 0.17-0.82),perform poorly.In terms of overall survival,progression-free survival,and objective response rate,the various interventions show similar effectiveness.In terms of safety,the regorafenib group has a lower probability of severe adverse reactions and death events than other interventions,indicating better safety.Compared to other interventions,the ramucirumab group has lower incidence of vomiting,hypertension,and diarrhea in specific adverse events,while there is little difference in the comparison of other interventions.3.In the comparison of three regimens,tenofovir alafenamide fumarate,tenofovir disoproxil fumarate and entecavir,for the treatment of chronic hepatitis B,the three regimens showed similar efficacy and safety,with tenofovir disoproxil fumarate performing better than entecavir in terms of virologic response(OR:0.56,95% CI:0.37-0.83).Conclusion:1.Combination regimens for systemic therapy of advanced hepatocellular carcinoma are generally better in terms of efficacy than the best recommended monotherapy regimen,sorafenib,over the past decade.Several emerging regimens did not outwardly outperform the previous preferred regimen of atezolizumab +bevacizumab in terms of effectiveness,but the combination of durvalumab and tremelimumab demonstrated a better safety profile,particularly in terms of the incidence of hypertension.2.For first line sorafenib treatment failure,the emerging treatment regimen did not show significant safety and efficacy advantages over the previously recommended regimen,regorafenib,which remains the more appropriate choice currently.For patients with comorbid underlying hypertension,ramucirumab is also a better choice than regorafenib because of its better safety profile in hypertension.3.In the treatment of patients with chronic hepatitis B,the overall effectiveness and safety of the three regimens do not differ significantly,but tenofovir disoproxil fumarate performs better than entecavir in terms of virologic response and is also the relatively better choice.