Efficacy of PD-1/PD-L1 inhibitors in advanced hepatocellular carcinoma: A systematic review and meta-analysis.

Objectives: This study aimed to investigate the efficacy and safety of programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: PubMed, EMBASE, and the Cochrane Library were searched for articles published until November 2022. Studies reporting the efficacy of PD-1/PD-L1 inhibitors in patients with advanced HCC were eligible for inclusion. The outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and ≥ Grade 3 treatment-related adverse events (TrAEs). Results: Fourteen trials with 4515 patients with HCC were included. Our results showed that treatment with PD-1/PD-L1 inhibitors was associated with better ORR and DCR than that with control (placebo or sorafenib or lenvatinib) (odds ratio [OR], 3.89; 95% confidence interval (CI), 2.55-5.95 and OR, 1.47; 95% CI, 1.11-1.95, respectively). The overall hazard ratio (HR) of PFS and OS were 0.66 (95% CI 0.56-0.78) and 0.65 (95% CI 0.55-0.77), respectively. In subgroup analysis, PD-1/PD-L1 inhibitor combination therapy had an advantage in terms of PFS (HR: 0.57 vs. 0.81) compared to that of PD-1/PD-L1 monotherapy. The incidence of grade 3-5 TrAEs was not significantly higher with PD-1/PD-L1 inhibitors than that with the control (OR, 1.12; 95% CI, 0.70-1.81). However, the combination of PD-1inhibitor with higher incidence of Grade 3-5 TrAEs (OR: 2.04, 95% CI 0.66-6.32) than the combination PD-L1 inhibitor (OR: 0.95, 95% CI 0.50-1.81). Conclusion: The combination of PD-1/PD-L1 inhibitors and targeted agents significantly improved the clinical outcomes in patients with advanced HCC. However, the incidence of Grade 3-5 TrAEs with PD-1 inhibitor combination therapy was higher than the combination PD-L1 inhibitor.

Efficacy and immunogenicity of insulin biosimilar compared to their reference products: a systematic review and meta-analysis.

BACKGROUND: To ascertain the efficacy, safety, and immunogenicity from existing evidence via conducting a meta-analysis of randomized controlled trials between biosimilar and originator insulins. METHODS: The PubMed, Cochrane Library, EMBASE, and ClinicalTrails.gov were searched to identify head-to-head randomized controlled trials (RCTs) that directly compare the efficacy and safety of biosimilar insulin and its originator. Efficacy was assessed by change of HbA1C, fasting plasma glucose (laboratory or self-monitoring of blood glucose (SMBG)), and change all mean of 7 points- or 8 points- SMBG. Safety was assessed by change in proportion hypoglycemia and serious hypoglycemia. The occurrence of anti-insulin antibodies (AIAs) was also evaluated. RESULTS: Fourteen RCTs with 6188 patients from different countries were included. Data were pooled using a random-effects model and were expressed as the mean difference (MD), odds ratio (OR), and 95% confidence interval (CI). In efficacy, Insulin biosimilar products showed similar in change of HbA1C at weeks 26 and 52, the MD were 0.03 (95% CI - 0.02 to 0.07, p = 0.28), and 0.05 (95% CI - 0.05 to 0.15, p = 0.36), respectively. The proportion of HbA1C less than 7% at endpoint, the OR were 1.04 (95% CI 0.89 to 1.20, p = 0.64). The change of fasting plasma glucose (laboratory or SMBG) mmol/L in 24-52 weeks and change all mean of 7 points-/8 points- SMBG mmol/L in 24-52 weeks, the MD were 0.02 (95% CI - 0.20 to 0.24, p = 0.87) and - 0.34 (95% CI - 1.35 to 0.67, p = 0.51), respectively. In occurrence of hypoglycemia (≥ 1 events) and severe hypoglycemia, the OR were 0.96 (95% CI 0.85 to 1.09, p = 0.52) and 1.06 (95% CI 0.85 to 1.31, p = 0.62). The AIA was 1.02 (95% CI 0.90 to 1.16, p = 0.76). Analysis stratified by type of diabetes and duration of insulin. There was no significant difference between the biosimilar and their reference group in a different type of diabetes and different duration of insulin. CONCLUSIONS: Insulin biosimilar showed comparable characteristics with the reference drug in terms of efficacy, safety, immunogenicity, through comprehensive and specific conventional meta-analysis.

Effectiveness of glutamine in the management of oral mucositis in cancer patients: a meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this meta-analysis was to evaluate the effectiveness of glutamine for preventing or treating moderate-to-severe oral mucositis induced by chemotherapy or radiation therapy in patients with cancer. METHODS: PubMed, Cochrane Library, and Embase were searched for eligible randomized controlled trials (RCTs) up to June 2020. The outcomes analyzed were oral mucositis (at all levels of severity). Data were pooled using the random-effects model and are expressed as risk ratios (RRs) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified using I2. RESULTS: Sixteen RCTs were included in this review. In this meta-analysis, compared with placebo, glutamine significantly reduced the incidence of grade 3 and 4 oral mucositis induced by chemotherapy or radiation therapy (RR, 0.53; 95% CI, 0.32-0.88). In subgroup analysis, oral glutamine administration (RR, 0.56; 95% CI, 0.34-0.92) and a medium or low daily dose of glutamine (RR, 0.58; 95% CI, 0.44-0.77; RR, 0.53; 95% CI, 0.28-0.94; respectively) decreased risk. Glutamine caused a borderline significant reduction in the risk of grade 3 and 4 oral mucositis induced by radiotherapy (RR, 0.75; 95% CI, 0.58-0.99) and especially in its prevention (RR, 0.51; 95% CI, 0.28-0.94). CONCLUSIONS: Glutamine significantly reduces the risk of oral mucositis during chemotherapy or radiation therapy. Furthermore, large prospective trials are required to support these findings.

Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies.

Background and objectives: The association between hypnotic drugs and risk of cancer remains controversial. Therefore, we performed a meta-analysis to investigate this association. Materials and Methods: Pubmed and Embase were searched systematically to identify publications up to April 2020. The Newcastle-Ottawa scale for observational studies was used to assess the quality of studies. All included studies were evaluated by two reviewers independently; any discrepancies were resolved through discussion. Results: Twenty-eight studies including 22 case-control studies and 6 cohort studies with 340,614 hypnotics users and 1,828,057 non-users were included in the final analyses. Hypnotics (benzodiazepines and Z-drugs) use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.17; 95% confidence interval 1.09-1.26) in a random-effects meta-analysis of all studies. Subgroup meta-analysis by anxiolytics/sedatives effect (anxiolytics benzodiazepines vs. sedatives group (include sedatives benzodiazepines and Z-drugs)) revealed that a significant association in sedatives group (pooled OR/RR 1.26, 95% CI, 1.10-1.45), whereas no significant relationship was observed in anxiolytics benzodiazepines (pooled OR/RR 1.09, 95% CI, 0.95-1.26). Moreover, a significant dose-response relationship was observed between the use of hypnotics and the risk of cancer. Conclusions: This meta-analysis revealed association between use of hypnotics drugs and risk of cancer. However, the use of lower dose hypnotics and shorter duration exposed to hypnotics seemed to be not associated with an increased risk of cancer. Moreover, the use of anxiolytics effect benzodiazepines seemed to be lower risk than sedatives benzodiazepines. A high heterogeneity was observed among identified studies, and results were inconsistent in some subgroups. Randomized control trials are needed to confirm the findings in the future.