scholarly journals Comparative Effectiveness and Safety of Seven Qi-Tonifying Chinese Medicine Injections for AECOPD Patients: A Systematic Review and Network Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xueyi Deng ◽  
Fuqin Kang ◽  
Xueyin Chen ◽  
Jiaqi Lai ◽  
Xuanchen Guan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chinese Medicine ◽  
Adverse Events ◽  
Comparative Effectiveness ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Small Sample ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Serious Adverse Events

Introduction. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) imposes a large burden on economy and society worldwide. In addition to western medicine, multiple kinds of qi-tonifying Chinese medicine injections have been widely used in China as adjunctive treatments. Previous small-sample clinical trials have proven their efficacy in the treatment of AECOPD. However, data on comparative effectiveness and safety of qi-tonifying injections are limited. We conducted this network meta-analysis to compare the efficacy and safety of 7 commonly used qi-tonifying injections in patients with AECOPD. Methods. Literature search was conducted through electronic databases, including PubMed, the Cochrane Library, EMBASE, CINAHL, AMED, CBM, CNKI, Wanfang database, and VIP database. Randomized clinical trials (RCTs) exploring the efficacy of any of these 7 qi-tonifying injections were included. The primary outcome was lung function (FEV1 and FVC). R 4.0.0 and STATA 12.0 were adopted to perform the network meta-analysis using Bayesian statistics. Results. A total of 36 RCTs involving 2657 participants were included. The results of network meta-analyses indicated that Chuankezhi injection (CKZ) combined with routine treatment (RT) was superior to other qi-tonifying injections combined with RT in terms of FEV1 improvement (MD = 0.63, 95% CI: 0.22, 1.04). For improving FVC, Shengmai injection (SGM) combined with RT showed the greatest therapeutic effect (MD = 0.38, 95% CI: 0.13, 0.61). Moreover, SGM combined with RT revealed the best estimates for response rate (MD = 4.00, 95% CI: 1.34, 13.63). The main adverse events in this study were gastrointestinal reactions and injection site reactions. No serious adverse events were reported. Conclusion. In this network meta-analysis, SGM and CKZ were potential best adjunctive therapies in the treatment of AECOPD.

scholarly journals Erenumab safety and efficacy in migraine: a systematic review and meta-analysis of randomized clinical trials

2018 ◽  
Author(s):  
Changyu Zhu ◽  
Jianmei Guan ◽  
Hua Xiao ◽  
Weinan Luo ◽  
Rongsheng Tong
Keyword(s):  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Specific Medication ◽  
Mean Differences

Abstract Background: Erenumab is a new medicine approved lately in the US for the preventive treatment of migraine in adults. We aimed to conduct a meta-analysis to evaluate the efficacy and safety of erenumab in patients with migraine. Methods: The electronic database composed of PubMed, Embase and Cochrane library was independently retrieved by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and erenumab were included in this analysis. mean differences (MDs) and Pooled risk ratios (RRs) as well as their corresponding 95% confidence intervals (CIs) were calculated for continuous and dichotomous data, respectively. Results: Total five RCTs representing 2928 patients were included. Pooled analysis showed significant reductions of the 50% reduction(RR 1.55; 95%CI,1.35 to 1.77; P < 0.00001; I²=49%). In addition, the mean monthly migraine days (MMMDs) from baseline in the erenumab group compared with placebo (MD -1.32, 95%CI, -1.73 to -0.91; P < 0.00001; I²=100%) and migraine-specific medication days (MSMDs) from baseline (MD -1.41; 95%CI, -1.80 to -1.02; P＜0.00001; I²=100%) were significantly increased for the erenumab group compared with placebo. Furthermore, there was significant reduction of MSMDs from baseline in 140mg erenumab group compared to 70mg (MD=0.55; 95%CI:0.54 to 0.66; Z =10.95; P<0.00001; I²=90% ). Finally, there were no significant differences between erenumab group and placebo of any adverse events and serious adverse events. Conclusion: Among patients with migraine, both 70mg and 140mg erenumab are associated with reduction of MMMDs, MSMDs from baseline and increased rate of 50% reduction without increased risk of any adverse events and serious adverse events.

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

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.

scholarly journals The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204209862110425
Author(s):  
Chenchula Santenna ◽  
Kota Vidyasagar ◽  
Krishna Chaitanya Amarneni ◽  
Sai Nikhila Ghanta ◽  
Balakrishnan Sadasivam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Antiviral Drug ◽  
Mortality Reduction ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Grade 3

Introduction: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. Methods: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as ‘COVID-19’ OR ‘SARS CoV-2’ AND ‘Remdesivir’. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. Results: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) ( n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40–0.74) p = 0.0001; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19–0.54) p = 0.0001; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59–1.11) p = 0.19; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 78%]. Discussion & Conclusion: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. Plain Language Summary Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo. The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir. There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir. There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

Abiraterone acetate (AA) or docetaxel (D) in metastatic castration-sensitive prostate cancer (mCSPC): A systematic review and network meta-analysis of randomized clinical trials (RCTs).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 243-243
Author(s):  
Irbaz Bin Riaz ◽  
Abdulaali Almutairi ◽  
Zeeshan Ali ◽  
Abdullah Alhifany ◽  
Sandipan Bhattacharjee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Random Effect ◽  
Indirect Comparison ◽  
Cochrane Library ◽  
Cochrane Central Register

243 Background: AA and D have been shown in separate trials to increase overall survival in patients with mCSPC compared to Androgen Derivation Therapy (ADT). In the absence of head to head clinical trials and to provide clinical guidance, we performed an indirect comparison of AA and D using network meta-analysis. Methods: We performed a search of MEDLINE, EMBASE, Cochrane Library, and Cochrane Central Register of Controlled Trials to identify relevant clinical trials. Collected data included hazard ratio and confidence interval (CI) for Overall Survival (OS) and number of adverse events in each study arm. Risk for bias was assessed using the Cochrane Collaboration’s tool. Bayesian network meta-analysis was conducted using WinBUGS 1.4.3 software (MRC Biostatistics Unit, Cambridge, UK) to perform an indirect comparison of D and AA. Results: Five clinical trials were included in this analysis. Two trials (LATITUDE, STAMPEDE) compared AA to ADT and three trials (CHAARTED,STAMPEDE, GETUG-AFU 15 study) compared D to ADT. Results from both fixed effect and random effect network meta-analyses for the primary outcome (OS) revealed no statistical significance between AA and D (HR 0.81,95%CI 0.65-1.01; HR 0.81, 95%CI 0.40-1.82) respectively. Comparatively, abiraterone had statistically significant fewer events of anemia (OR 0.14,95%CI 0.08-0.23), neutropenia (OR 0.06,95%CI 0.03-0.12), peripheral edema (OR 0.21,95%CI 0.09-0.44), dyspnea (OR 0.22,95%CI 0.08-0.51), nausea (OR 0.09,95%CI 0.02-0.24), diarrhea (OR 0.06,95%CI 0.02-0.15), constipation (OR 0.25,95%CI 0.11-0.53), and fatigue (OR 0.12,95%CI 0.07-0.20). AA had statistically significant more events of hot flashes (OR 3.85, 95% CI2.33-6.25). For other adverse events, both drugs were statistically similar. Conclusions: There is no difference in OS using AA for longer periods in CSPC than a regimen of a limited number of cycles of D. There are significant differences in side effect profile of these drugs. Further analyses are needed to determine cost effectiveness of AA vs D under consideration of comparative efficacy and safety.

scholarly journals The effects of adding glucocorticosteroids to standard care for children with sepsis. A systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis

2021 ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sanam Safi ◽  
Christian Gluud ◽  
Janus C Jakobsen
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Standard Care ◽  
Sequential Analysis ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
Meta Analyses

Abstract Background: Glucocorticosteroids are widely used to treat severe sepsis in pediatric intensive care units. However, the evidence on the clinical effects is unclear.Objective: To assess the benefits and harms of glucocorticosteroids for children with sepsis. Data Sources: We conducted a systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis (TSA) (PROSPERO CRD42017054341). We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, and more. Study Selection: Randomized clinical trials assessing the effects of adding glucocorticosteroids to standard care for children with sepsis. Data Extraction: Two independent reviewers screened studies and extracted data. Evidence was assessed by GRADE according to our published protocol.Data Synthesis: We included 24 trials randomizing 3073 participants. Meta-analyses showed no evidence of an effect of adding glucocorticosteroids for children with sepsis with a mixed focus for any of our outcomes. Meta-analyses suggested evidence of a beneficial effect of dexamethasone for children with meningitis when assessing serious adverse events (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.53 to 0.86; P = 0.001, very low certainty of evidence) and ototoxicity (RR 0.63, 95% CI 0.45 to 0.88; P = 0.007, low certainty of evidence). TSAs showed that we did not have sufficient data to confirm or reject these results. We found insufficient evidence to confirm or reject an effect on mortality or our other outcomes. No trials reported quality of life or organ failure. Most trials were at high risks of bias. We found high clinical heterogeneity between participants. None of our TSAs showed benefits, harms or futility. Conclusions: Generally, we found no evidence of an effect of glucocorticosteroids for children with sepsis without meningitis. Dexamethasone for sepsis in children due to meningitis may decrease serious adverse events and ototoxicity.

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

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.

675 FUNDOPLICATION VERSUS ORAL PROTON PUMP INHIBITORS FOR GASTROESOPHAGEAL REFLUX DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Luca Schiliró Tristão ◽  
Francisco Tustumi ◽  
Guilherme Tavares ◽  
Letícia Nogueira Datrino ◽  
Maria Carolina Andrade Serafim ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Adverse Events ◽  
Proton Pump ◽  
Reflux Disease ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Oral Intake

Abstract   Gastroesophageal reflux disease (GERD) is a widely studied and highly prevalent condition. However, few is reported about the exact efficacy and safety of fundoplication (FPT) compared to oral intake proton-pump inhibitors (PPI). This systematic review and meta-analysis of randomized clinical trials (RCT) aims to compare PPI and FPT in relation to the efficacy, as well as the adverse events associated with these therapies. Methods This systematic review was guided by PRISMA statement. Search carried out in June 2020 was conducted on Medline, Cochrane, EMBASE and LILACS. The inclusion criteria were (I) patients with GERD; (II) Randomized clinical trials, comparing oral intake PPI with FPT; (III) relevant outcomes for this review. The exclusion criteria were (I) reviews, case reports, editorials and letters (II) transoral or endoscopic FPT (III) studies with no full text. No restrictions were set for language or period. Certainty of evidence and risk of bias were assessed with GRADE Pro and with Review Manager Version 5.4 bias assessment tool. Results Ten RCT were included. Meta-analysis showed that heartburn (RD = −0.19; 95% CI = −0.29, −0.09) was less frequently reported by patients that underwent FPT. Furthermore, patients undergoing surgery had greater pressure on the lower esophageal sphincter than those who used PPI (MD = 7.81; 95% CI 4.79, 10.83). There was no significant difference between groups in the percentage of time with pH less than 4 in 24 hours, sustained remission and Gastrointestinal Symptom Rating Scale. Finally, FPT did not increase significantly the risk for adverse events such as postoperative dysphagia and impaired belching. Conclusion FPT is a more effective therapy than PPI treatment for GERD, without significantly increasing the risk for adverse events. However, before indicating a possible surgical approach, it is extremely important to correctly assess and select the patients who would benefit from FPT, such as those with severe erosive esophagitis, severe respiratory symptoms, low adherence to continuous drug treatment and patients with non-acid reflux, to ensure better results.

Abstract P391: Marine N-3 Fatty Acids Reduce Atherosclerosis Cardiovascular Disease: A Systemic Review and Meta-analysis of Clinical Trials

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Akira Sekikawa ◽  
Nobutake Hirooka ◽  
Abhishek Vishnu ◽  
Vashudha Ahuja ◽  
Emmanuel Sampene ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Imaging Techniques ◽  
Meta Analysis ◽  
Quantitative Information ◽  
Systemic Review ◽  
Cochrane Library ◽  
Cardiac Imaging Techniques

Introduction: Although marine n-3 fatty acids are believed to be cardioprotective through their anti-arrhythmic, anti-thrombotic, anti-atherogenic and other effects, results from recent meta-analyses of marine n-3 fatty acids on cardiovascular disease (CVD) are controversial. We performed a meta-analysis of marine n-3 fatty acids on CVD outcomes in randomized clinical trials (RCTs) to test the hypothesis that marine n-3 fatty acids are anti-atherogenic. We also tested the hypothesis that such benefit is dose-dependent. Methods: A systematic review of English language articles using PubMed, EMBASE and Cochrane Library through Aug 2012 was performed selecting RCTs evaluating the effect of marine n-3 fatty acids intake for 2 years or more on cardiovascular diseases, coronary disease, arteriosclerosis, cardiac imaging techniques, and carotid artery ultrasound. Descriptive and quantitative information was extracted. Odds ratios were calculated for cardiac event outcome. Correlation coefficients were obtained from studies of which outcome is intima-media thickness (IMT) and coronary lumen diameter (CD). We converted the estimates into a single effect size; the log odds ratio and its corresponding standard error. Results: Of 14,236 citations retrieved, 13 studies were selected, including studies reporting IMT (n=3) and CD (n=2) and major CVD events (n=8). Overall, marine n-3 fatty acids significantly reduced atherosclerotic CVD (RR 0.94: 95%CI 0.90 to 0.99, p<0.05). There was no evidence of heterogeneity (p=0.65) or publication bias (p=0.37, Begg’s test). A sub-analysis among 8 studies of major CVD events showed the similar results (RR 0.94: 95% CI 0.89 to 0.99, p<0.05). Another sub-analysis among 4 studies excluding sudden cardiac death as an outcome showed RR of 0.91 (95% CI 0.82 to 1.02, p=0.097). A meta-regression analysis shows that dose of marine n-3 fatty acids was inversely associated with CVD outcome, although the association was not statistically significant (p=0.06). Conclusions: The result of our meta-analysis supports a modest anti-atherogenic effect of marine n-3 fatty acids. This benefit may be proportional to the amount of marine n-3 fatty acids consumed.

scholarly journals Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Sunil Badami ◽  
Sunil Upadhaya ◽  
Ravi Kanth Velagapudi ◽  
Pushyami Mikkilineni ◽  
Ranju Kunwor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Random Effect ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Melanoma ◽  
Cochrane Library ◽  
Molecular Characteristics ◽  
Significant Heterogeneity

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

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