PP264 Effectiveness And Safety Of Pressurized Intraperitoneal Aerosol Chemotherapy For Peritoneal Carcinomatosis: A Systematic Review

IntroductionPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a minimally invasive therapeutic option for stage IV or terminal stage peritoneal carcinomatosis, which has a very low survival rate. PIPAC is aimed at patients whose only therapeutic alternative is systemic chemotherapy because they are unable to undergo other treatments, such as cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. PIPAC consists of a micro-pump connected to a double-contrast injector, which is used to apply cytotoxic agents laparoscopically using pressurized aerosols. The objective of this study was to update the evidence regarding the effectiveness and safety of PIPAC.MethodsA systematic review (SR) was conducted by searching PubMed, Embase, and The Cochrane Library database. ClinicalTrials.gov and the European Union Drug Regulating Authorities Clinical Trials Database were consulted to identify registered clinical studies. All articles published up to April 2019 were considered for inclusion. Abstracts, letters, single case studies, non-clinical and animal studies, and studies published in languages other than English or Spanish were excluded. Validated checklists were used to assess the quality of the included studies.ResultsSeventeen studies were included (three SRs and fourteen cases series) and eighteen ongoing clinical trials were identified. The quality of the SRs and cases series studies was low and moderate, respectively. Adverse events were categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events as grade 1–2 (mild-moderate: 11% to 40% of patients) and grade 3–4 (severe-fatal: 0% to 37% of patients). Overall complete histological regression according to the Peritoneal Regression Grading Score and the Peritoneal Cancer Index occurred in at least sixty percent of patients. The survival time ranged from 11 to 16 months.ConclusionsEffectiveness data for PIPAC were promising, with high carcinomatosis regression rates. Most studies showed a moderate safety profile, with generally mild to moderate complications (nausea, abdominal pain, and vomiting). This is an advantage over systemic chemotherapy, which has severe systemic side effects. Economic evaluation studies are needed to estimate the cost effectiveness and cost utility of this technology. Diffusion of PIPAC is expected, but the criteria used to select patients in the studies carried out so far must be considered, as well as the need to follow strict safety protocols for preventing leakage of aerosolized cytotoxic drugs.

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Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽

10.3390/vaccines9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Jiaxin Chen ◽

Yuangui Cai ◽

Yicong Chen ◽

Anthony P. Williams ◽

Yifang Gao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Fixed Effects ◽

Meta Analysis ◽

Phase 1 ◽

Cochrane Library ◽

Categorical Variables ◽

Control Group ◽

Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

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Opioids in Post-stroke Pain: A Systematic Review and Meta-Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2020.587050 ◽

2020 ◽

Vol 11 ◽

Author(s):

Damiana Scuteri ◽

Elisa Mantovani ◽

Stefano Tamburin ◽

Giorgio Sandrini ◽

Maria Tiziana Corasaniti ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Dose Response ◽

Analgesic Effect ◽

Literature Search ◽

Meta Analysis ◽

Cochrane Library ◽

Post Stroke ◽

Pain Syndromes

Background: Post-stroke pain is one of the most common sequelae of stroke, which stands among the leading causes of death and adult-acquired disability worldwide. The role and clinical efficacy of opioids in post-stroke pain syndromes is still debated.Objectives: Due to the important gap in knowledge on the management of post-stroke pain, this systematic review aimed at assessing the efficacy of opioids in post-stroke pain syndromes.Methods: A literature search was conducted on databases relevant for medical scientific literature, i.e. PubMed/MEDLINE, Scopus, Web of Science and Cochrane Library databases from databases inception until August 31st, 2020 for clinical trials assessing the effects of opioids and opioid antagonists on pain reduction and pain related symptoms in patients with post-stroke pain syndromes. Studies assessing the effects of other medications (e.g., tricyclic antidepressant, pregabalin) or non - pharmacological management strategies (e.g., neurostimulation techniques) were excluded. The selected studies have been subjected to examination of the risk of bias.Results: The literature search retrieved 83,435 results. After duplicates removal, 34,285 articles were title and abstract screened. 25 full texts were assessed and 8 articles were identified to be eligible for inclusion in the qualitative summary and narrative analysis, of which three were placebo-controlled and two were dose-response. Among placebo-controlled studies, two evaluated the analgesic effect of morphine and one assessed the effects of the opioid antagonist naloxone on patients with central post-stroke pain. With regard to dose-response studies, both were on patients with central post-stroke pain, one assessing the efficacy of levorphanol, and the other on naloxone. Seven out of eight included studies showed an overall slight analgesic effect of opioids, with less consistent effects on other pain-related symptoms (e.g., mood, quality of life). The randomized controlled trials were subjected to meta-analysis and rating of the quality of evidence for the two outcomes considered according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations) system. The overall results are inconclusive because of the small number of studies and of patients.Conclusions: The limited number of the included studies and their heterogeneity in terms of study design do not support the efficacy of opioids in post-stroke pain and in pain-related outcomes. Large double-blind randomized clinical trials with objective assessment of pain and related symptoms are needed to further investigate this topic.

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Repurposing of drugs for Covid-19: a systematic review and meta-analysis

10.1101/2020.06.07.20124677 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pinky Kotecha ◽

Alexander Light ◽

Enrico Checcucci ◽

Daniele Amparore ◽

Cristian Fiori ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Clinical Improvement ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Cochrane Library ◽

Control Group ◽

Significant Difference

AbstractObjectiveThe aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.MethodsWe searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).ResultsFrom 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power.DiscussionDue to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)

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Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms

Frontiers in Immunology ◽

10.3389/fimmu.2021.670398 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yi Ru ◽

Xiaojie Ding ◽

Ying Luo ◽

Hongjin Li ◽

Xiaoying Sun ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Event ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Cochrane Library ◽

The Cochrane Library ◽

Specific Symptoms

BackgroundAnti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed.ObjectivesThe aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents.MethodsThe Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events.ResultsForty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events.ConclusionsThe application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles.

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Gastric cancer: modern approaches and prospects of treatment for peritoneal carcinomatosis (literature review)

Siberian Journal of Oncology ◽

10.21294/1814-4861-2021-20-6-104-113 ◽

2022 ◽

Vol 20 (6) ◽

pp. 104-113

Author(s):

V. A. Markovich ◽

S. A. Tuzikov ◽

E. O. Rodionov ◽

N. V. Litvyakov ◽

N. O. Popova ◽

...

Keyword(s):

Gastric Cancer ◽

Peritoneal Carcinomatosis ◽

Intraperitoneal Chemotherapy ◽

Cytoreductive Surgery ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

Systemic Chemotherapy ◽

Antitumor Agents ◽

Peritoneal Cancer Index ◽

Abdominal Cavity ◽

Cochrane Library

Gastric cancer (gc) is one of the most common cancers worldwide. The majority of newly diagnosed gastric cancer cases present with distant metastases. Peritoneal carcinomatosis (pc) is the most unfavorable type of progression of primary gc, which occurs in 14–43 % of patients. The purpose of the study was to highlight modern approaches to the treatment of gc with pc. Material and methods. We analyzed 136 publications available from pubmed, medline, cochrane library, and elibrary databases. The final analysis included 46 studies that met the specified parameters. Results. The modern approaches to the treatment of gc with peritoneal carcinomatosis were reviewed, namely: cytoreductive surgery (crs), combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (crs/hipec); neoadjuvant intraperitoneal/systemic chemotherapy (nips) and pressurized intraperitoneal aerosol chemotherapy (pipac). The results of large randomized trials and meta-analyses were analyzed. Benefits and limitations of these trials were assessed. Conclusion. The peritoneal cancer index (pci) and the level of cytoreduction are two key prognostic factors for increasing the median overall survival. By reducing tumor volume through cytoreductive surgery, it is possible to allow tumor cells to re-enter the proliferative phase of the cell cycle and make them more sensitive to antitumor agents. The hematoperitoneal barrier is the main reason that prevents the effective delivery of drugs from the systemic bloodstream to the abdominal cavity, which is why the effect of systemic chemotherapy on peritoneal metastases is extremely limited. Intraperitoneal chemotherapy offers a more effective and intensive regional therapy, creating a so-called «depot» of a chemotherapy drug, thereby prolonging the effect of the administered drugs. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (crs + hipec) using the combination of surgical resection, cytotoxic chemotherapy, hyperthermic ablation of the tumor and hydrodynamic flushing, is a promising approach in the treatment of gc with peritoneal carcinomatosis.

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Effects of mindfulness-based interventions on quality of life of women with breast cancer: a systematic review

Journal of Comparative Effectiveness Research ◽

10.2217/cer-2019-0053 ◽

2019 ◽

Vol 8 (11) ◽

pp. 829-840 ◽

Cited By ~ 2

Author(s):

Xinyan Zhang ◽

Dongling Liu ◽

Yuxiang Li ◽

Ye Zhang ◽

Bingyan Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Systematic Review ◽

Adverse Events ◽

Stress Reduction ◽

Quality Index ◽

Web Of Science ◽

Cochrane Library ◽

Good Effect

Aim: The systematic review assessed the effect of mindfulness-based interventions on the quality of life among women with breast cancer. Methods: PubMed, Cochrane library, EMBASE, Web of Science and CINAHL databases were searched for studies published. Our review assessed the effect of mindfulness-based interventions (Mindfulness-Based Stress Reduction [MBSR] intervention and Mindfulness-Based Cognitive Therapy [MBCT]) on quality of life for women with breast cancer. Two authors independently assessed the quality of all included studies using the Downs and Black Quality Index. Results: The search finally identified 15 studies. The MBSR intervention showed a significant effect between groups. The MBCT intervention also showed good effect on quality of life. Adverse events were inadequately reported. Conclusion: The MBSR intervention on quality of life among women with breast cancer was effective and safe. The effect of MBCT intervention on quality of life still needs more research.

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Intervention Therapies to Reduce Pain-Related Fear in Fibromyalgia Syndrome: A Systematic Review of Randomized Clinical Trials

Pain Medicine ◽

10.1093/pm/pnaa331 ◽

2020 ◽

Author(s):

Javier Martinez-Calderon ◽

Mar Flores-Cortes ◽

Jose Miguel Morales-Asencio ◽

Alejandro Luque-Suarez

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Risk Of Bias ◽

Cochrane Library ◽

Secondary Outcome ◽

Full Detail ◽

Eligibility Criteria ◽

Fear Avoidance Beliefs

Abstract Objective This systematic review aimed to evaluate the effectiveness of different interventions at reducing pain-related fear in people with fibromyalgia and to analyze whether the included trials reported their interventions in full detail. Design Systematic review. Setting No restrictions. Methods The Cochrane Library, CINAHL, EMBASE, PsycINFO, PubMed, and Scopus were searched from their inception to April 2020, along with manual searches and a gray literature search. Randomized clinical trials were included if they assessed pain-related fear constructs as the primary or secondary outcome in adults with fibromyalgia. Two reviewers independently performed the study selection, data extraction, risk-of-bias assessment, Template for Intervention Description and Replication (TIDieR) checklist assessment, and grading the quality of evidence. Results Twelve randomized clinical trials satisfied the eligibility criteria, including 11 cohorts with a total sample of 1,441 participants. Exercise, multicomponent, and psychological interventions were more effective than controls were in reducing kinesiophobia. However, there were no differences in decreasing kinesiophobia when self-management and electrotherapy were used. There were also no differences between groups with regard to the rest of the interventions and pain-related constructs (fear-avoidance beliefs, fear of pain, and pain-related anxiety). However, a serious risk of bias and a very serious risk of imprecision were detected across the included trials. This caused the overall certainty of the judged evidence to be low and very low. Additionally, the included trials reported insufficient details to allow the full replication of their interventions. Conclusions This systematic review shows that there are promising interventions, such as exercise, multicomponent, and psychological therapies, that may decrease one specific type of fear in people with fibromyalgia, i.e., kinesiophobia. However, because of the low–very low certainty of the evidence found, a call for action is needed to improve the quality of randomized clinical trials, which will lead to more definitive information about the clinical efficacy of interventions in this field.

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Sublingual immunotherapy for pollen allergic rhinitis: a systematic review and meta-analysis

10.22541/au.160642445.59361931/v1 ◽

2020 ◽

Author(s):

Lufang Feng ◽

Liujiao Cao ◽

Peijing Yan ◽

Xiajing Chu ◽

Na Zhang ◽

...

Keyword(s):

Systematic Review ◽

Allergic Rhinitis ◽

Adverse Events ◽

Sublingual Immunotherapy ◽

Meta Analysis ◽

Gastrointestinal Symptoms ◽

Specific Ige ◽

Cochrane Library ◽

Serious Adverse Events

Intro Allergic rhinitis（AR） is a common condition which can significantly impair quality of life. This study aimed to illustrate the efficacy and safety of sublingual immunotherapy (SLIT) on pollen AR patients. Methods Four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from their inception until September 2019. Two reviewers （FLF and CLJ） independently extracted the data. The Cochrane’s Risk of Bias tool was used to assess the quality of included studies. The outcomes of study were calculated by MD or SMD with 95%CI. A meta-analysis was performed using RevMan 5.3 software. Results In this systematic review, a total of 8 articles were included, involving 785 participants. The quality of the included studies ranged from low to moderate. The results of the meta-analysis showed that compared with placebo, a significant reduction of nasal symptoms were observed on SLIT (MD = −0.84, 95% CI = −1.47 to −0.22, P < 0.05), IgE (SMD =0.46, 95% CI = 0.16 to 0.76, P < 0.05); No significant effect on medication scores (MD = −0.41, 95% CI = −0.89 to 0.07, P =0.10). No serious adverse events were reported, and symptoms of adverse events were reported more frequently in the gastrointestinal symptoms. Conclusion SLIT can effectively relieve rhinitis symptoms and decrease the level of specific-IgE for pollen allergic rhinitis patients and the safety was verified. But due to the low quality of studies, more high-quality randomized trials are needed to provide stronger evidence of the conclusion.

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Anti-hypertensive drugs deprescribing: an updated systematic review of clinical trials

BMC Family Practice ◽

10.1186/s12875-021-01557-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Salvatore Crisafulli ◽

Nicoletta Luxi ◽

Raffaele Coppini ◽

Annalisa Capuano ◽

Cristina Scavone ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Experimental Studies ◽

Risk Of Bias ◽

Cochrane Library ◽

Efficacy And Safety ◽

Systematic Assessment ◽

Grade Approach

Abstract Background Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs. Methods MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool. Results Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk. Conclusions This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients.

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First-Line Systemic Treatment Strategies for Unresectable Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

Frontiers in Oncology ◽

10.3389/fonc.2021.771045 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wenfeng Liu ◽

Bing Quan ◽

Shenxin Lu ◽

Bei Tang ◽

Miao Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Cochrane Library ◽

Cochrane Central Register ◽

First Line ◽

Unresectable Hepatocellular Carcinoma

ObjectiveSeveral new first-line treatments were recently approved for unresectable hepatocellular carcinoma (HCC). In this meta-analysis, we compare the efficacy and safety of first-line systemic treatments to provide information for clinical decision making in unresectable HCC.MethodsPubmed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, Embase, Google Scholar, the Cochrane Library, EMbase, CNKI, CBM, VIP, and the Wanfang databases, as well as the Cochrane Central Register of Controlled Trails were searched for randomized clinical trials evaluating the efficacy of first-line chemotherapy, molecular targeted therapy, or immunotherapy for unresectable HCC. Hazard ratios with 95% confidence intervals (CIs) were calculated to explore the effects of various treatment options on overall survival (OS) and progression-free survival (PFS), whereas odd ratios with 95% CIs were used for adverse events (AEs) and serious adverse events (SAEs). A network meta-analysis was performed to synthesize data and for direct and indirect comparisons between treatments. The cumulative ranking curve (SUCRA) and P score were used to rank treatments. The risk of bias across studies was assessed graphically and numerically using the funnel plot and Egger’s regression test.ResultsFifteen studies including 9005 patients were analyzed. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, and donafenib had better OS outcomes than sorafenib. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, lenvatinib, and linifanib had better PFS outcomes than sorafenib. The results of network meta-analysis showed that sintilimab plus bevacizumab was associated with the best OS and PFS. Egger’s tests indicated that none of the included studies had obvious publication deviation.ConclusionSintilimab plus bevacizumab showed the best OS and PFS outcomes with no additional AEs or SAEs. Thus, sintilimab plus bevacizumab may be a better first line choice for the treatment of patients with unresectable HCC.Systematic Review RegistrationPROSPEROI [https://www.crd.york.ac.uk/PROSPERO/index.php], identifier CRD42021269734.

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