scholarly journals Rheumatic immune-related adverse events associated with immune checkpoint inhibitors compared with placebo in oncologic patients: a systemic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204062232097699
Author(s):  
Shuo Zhang ◽  
Ziyue Zhou ◽  
Li Wang ◽  
Mengtao Li ◽  
Fengchun Zhang ◽  
...  
Keyword(s):  
Relative Risk ◽  
Adverse Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Systemic Review ◽  
Placebo Control ◽  
Oncologic Patients

Objective: We aim to characterize the incidence and relative risk of rheumatic and systemic immune-related adverse effects (irAEs) among immune checkpoint inhibitor (ICI) therapy compared with those after placebo treatment. Methods: Randomized clinical trial studies with placebo control with the following keywords were searched from Embase, PubMed, Cochrane databases: immune checkpoint inhibitors, neoplasms, randomized controlled trials, and adverse effects. Results: Among the 5444 published and 316 registration records, nine placebo-controlled randomized clinical trials met our selection criteria, and included data from 5560 patients. Compared with placebo use, using ICIs increases the risk of overall-rheumatic irAEs. The incidence and relative risk of all-grade rheumatic irAEs were 18.40% [95% confidence interval (CI) 12.16–25.59%, p < 0.01] and 2.30 (95% CI 1.32–4.02), respectively, while musculoskeletal irAEs were 11.30% (95% CI 9.76–12.85%) and 1.01 (95% CI 0.84–1.22). The incidence and relative risk of severe rheumatic irAEs were 5.72% (95% CI 3.92–7.82%), and 8.29 (95% CI 3.75–18.35), respectively. Arthralgia was the most common rheumatic irAE (incidence 11.00%, 95% CI 9.55–12.64%; relative risk 0.99, 95% CI 0.82–1.19), although usually not severe. Colitis (incidence 3.23%, 95% CI 1.27–7.98%; relative risk 6.53, 95% CI 2.66–16.04) and pneumonitis (incidence 3.11%, 95% CI 1.56–6.21; relative risk 4.04, 95% CI 1.65–9.89) were commonly observed and tended to be severe. Hepatitis, hypophysitis, thyroiditis, and myositis were rare and less recorded, yet can be severe and life threatening. Other extremely rare severe rheumatic irAEs included sarcoidosis ( n = 11), autoimmune arthritis ( n = 8), autoimmune uveitis ( n = 3), autoimmune pericarditis, bursitis, osteochondrosis, psoriasis, polymyalgia rheumatica, systemic inflammatory response syndrome, and Sjögren syndrome ( n = 1, each). Conclusion: ICI therapy increased the incidence and relative risk of all-grade and severe rheumatic irAEs. Arthralgia was the most commonly observed non-severe irAE, while colitis and pneumonitis were commonly observed severe irAEs. Rare rheumatic irAEs like hepatitis, hypophysitis, thyroiditis, and myositis warrant special attention.

scholarly journals 41P Cardiotoxicity of immune checkpoint inhibitors: A meta-analysis of randomized clinical trials

2020 ◽  
Vol 31 ◽  
pp. S1432
Author(s):  
E. Agostinetto ◽  
D. Eiger ◽  
M. Lambertini ◽  
M. Ceppi ◽  
M. Bruzzone ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis

scholarly journals Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials

2018 ◽  
Author(s):  
Antonino Grassadonia ◽  
Isabella Sperduti ◽  
Patrizia Vici ◽  
Laura Iezzi ◽  
Davide Brocco ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
Cochrane Central Register

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p&lt;0.001 and HR 0.77, p&lt;0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p&lt;0.012), with the exception of melanoma (in women, HR 0.80, p=0.006). PFS was longer in men than in women (HR 0.67, p&lt;0.001 and HR 0.77, p=0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.

Cardiovascular toxicity incidence following immune checkpoint inhibitors in randomized clinical trials: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2636-2636
Author(s):  
Camila Bragança Xavier ◽  
Carlos Diego Holanda Lopes ◽  
Guilherme Harada ◽  
Artur Katz ◽  
Denis Leonardo Fontes Jardim
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Increased Risk ◽  
Meta Analyses

2636 Background: Immune checkpoint inhibitors (ICIs) are widely used in oncology and may be associated with a variety of immune-related toxicities. Cardiovascular (CV) adverse effects (AEs) are underreported in randomized clinical trials (RCTs), and the real risk associated with ICIs use has yet to be defined. Therefore, we aimed to investigate the incidence and risk of cardiovascular toxicities in patients receiving ICIs, using an up-to-date meta-analysis of prospective RCTs. Methods: We conducted a systematic search of the literature from January 1st, 2010 until July 1st, 2020 to identify RCTs testing ICIs for solid tumors, either in monotherapy or in combination between them. Our initial search yielded a total of 21,249 relevant publications. For CV AEs incidence estimation, we included phase III RCTs testing PD-1, PD-L1, CTLA-4 inhibitors or any combination of these agents. For relative risk (RR) assessment, we included phase II or phase III RCTs testing the same agents and with placebo or best supportive care (BSC) as the comparator. Data were extracted by independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. CV AEs were categorized based on the Common Toxicity Criteria (CTCAE) and stratified by ICIs type. Analyses were conducted using random effects model. Results: After screening and eligibility assessment, a total of 21,118 patients (67 cohorts from 57 trials) were available for this meta-analysis. We categorized the cohorts by ICIs regimen as monotherapy with a PD-1 inhibitor (35 cohorts; 10,241 patients), PD-L1 inhibitor (12 cohorts; 3,755 patients), CTLA-4 inhibitor (11 cohorts; 4,135 patients), and combination therapy (9 cohorts; 2,987 patients). Incidence measures are described in the table. Deaths from any CV cause occurred in 0.20% of the patients (95%CI 0.10%; 0.20%). For RR analysis, we included 12 cohorts from 11 RCTs. Risk of experiencing all grade AEs was numerically higher among patients who received ICIs than placebo or BSC (RR 1.16; 95%CI 0.98; 1.37; p=0.09). When only grade 3-5 CV AEs were considered, ICIs were associated with increased risk (RR 1.36; 95%CI 1.06; 1.73; p= 0.01). Additional analyses were conducted to estimate the RR of individual CV AEs including arrhythmia, cardiac arrest, heart failure, stroke, hypertension, myocardial infarction, myocarditis, pericardial events, and thromboembolic events. None of the analysis identified a significant additional risk. Conclusions: This meta-analysis corroborates the preclinical rationale of worsen CV risk related to ICIs use.[Table: see text]

Does radiation increase the risk of immunotherapy related pneumonitis in cancer patients with thorax radiotherapy combined immune checkpoint inhibitors: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15099-e15099
Author(s):  
Yamin Jie ◽  
Anxin Gu ◽  
Pingfu Fu ◽  
Feng-Ming Spring Kong
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Control Group ◽  
Chi Square ◽  
Chi Square Test ◽  
Newcastle Ottawa Scale

e15099 Background: Thorax radiotherapy (TRT) combined with immunotherapy has shown promising results. However, it remains unclear whether TRT would increases the risk of immunotherapy related pneumonitis (IRP). Here, we performed a meta-analysis to compare the rates of IRP in patients treated with TRT to patients treated without TRT. Methods: A meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Two individual researchers conducted the platform searches on the PubMed upto Nov. 4th, 2019. Quality of studies was assessed independently by two researchers using the Cochrane Collaboration's tool for randomized clinical trials, and the Newcastle-Ottawa Scale for cohort studies. Any disagreements encountered were settled through senior authors. The single rate of pneumonitis along with the corresponding 95% confidence interval (CI) was estimated. The odds ratio (OR) and its 95% CI were computed using random-effects model after checking the heterogeneity across studies using the Cochran Q chi-square test and the I2 statistic. Data analyses were performed using R version 3.6.2, meta and metafor packages. Results: A total of 62 studies including 14648 patients on IRP were first selected. Thirteen studies had two arms data, 501 patients were in TRT arm, 1185 patients were in non-TRT arm. Two studies including 557 patients were treated with immunotherapy and concurrent/sequential TRT. The remaining 47 studies had no TRT patients or TRT data were unavailable. The pooled rate of any grade IRP of all 62 studies (14648 patients) was 6% (95% CI: 5%-8%). All grades IRP was significantly higher among patients treated with immunotherapy and TRT arm when compared to the non-TRT arm (OR = 1.44, 95% CI: 1.04-2.00, P = 0.030). In the subgroup analysis, no significance difference in IRP rate was found between patients with various cancer types or various types of immune checkpoint inhibitors (p = 0.7033, p = 0.7522, respectively). The rate of IRP in all TRT patients was 18% (95% CI: 13%-24%), comparing to 5% (95% CI: 4%-6%) in control group. Conclusions: This meta-analysis demonstrates that TRT combined immunotherapy had an elevated incidence of IRP compared to non-TRT (OR = 1.44, 95% CI: 1.04-2.00, P = 0.030). There remains a lack of data on risk factors of IRP in TRT patients, and future large-scale studies are warranted. To our knowledge, this is the first comprehensive meta-analysis of IRP for TRT patients.

scholarly journals Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials

2018 ◽  
Vol 7 (12) ◽  
pp. 542 ◽  
Author(s):  
Antonino Grassadonia ◽  
Isabella Sperduti ◽  
Patrizia Vici ◽  
Laura Iezzi ◽  
Davide Brocco ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
Cochrane Central Register

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p < 0.001 and HR 0.77, p < 0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p < 0.012), with the exception of melanoma (in women, HR 0.80, p = 0.006). PFS was longer in men than in women (HR 0.67, p < 0.001 and HR 0.77, p = 0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.

scholarly journals Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials

2018 ◽  
Author(s):  
Antonino Grassadonia ◽  
Isabella Sperduti ◽  
Patrizia Vici ◽  
Laura Iezzi ◽  
Davide Brocco ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
Cochrane Central Register

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p&lt;0.001 and HR 0.77, p&lt;0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p&lt;0.012), with the exception of melanoma (in women, HR 0.80, p=0.006). PFS was longer in men than in women (HR 0.67, p&lt;0.001 and HR 0.77, p=0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.

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