scholarly journals Carfilzomib-associated cardiovascular adverse events: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8018-8018 ◽  
Author(s):  
Adam Justin Waxman ◽  
Suparna Chandra Clasen ◽  
Alfred L. Garfall ◽  
Joseph R. Carver ◽  
Dan T. Vogl ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Adverse Events ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Phase 1 ◽  
Incidence Rates ◽  
Optimal Monitoring ◽  
Study Characteristics ◽  
Grade 3

8018 Background: The incidence and nature of cardiovascular adverse events (CVAEs) with carfilzomib (CFZ) in multiple myeloma (MM) remain incompletely defined. We performed the first systematic review and meta-analysis of CFZ CVAEs. Methods: PubMed was queried for the keywords “carfilzomib,” “Kyprolis,” and “PX-171.” Phase 1-3 clinical trials of carfilzomib in MM with evaluable toxicity data were included. CVAEs were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grade ≥3 CVAEs and study characteristics were recorded. Summary incidence rates and relative risks (for randomized trials) with 95% confidence intervals were calculated using the logistic-normal random-effects model. Subgroup analyses were performed using study level covariates. Results: 514 studies were reviewed. 2623 MM patients from 25 eligible studies were included. Incidence rates are summarized in the table. All grade and grade ≥3 CVAEs were seen in 16.8% and 7.6 %, respectively. Phase 2 or 3 studies, carfilzomib doses ≥45mg/m2, and longer infusion length were study characteristics associated with high-grade cardiac AEs (p<0.05). Median age >65, prior MM therapies, and concurrent MM therapies were not associated with CVAEs (p>.05). For the three randomized trials, the relative risk of all-grade and grade ≥3 CVAEs were 1.75 and 2.25, respectively (p<0.001). Conclusions: CFZ is associated with a significant incidence of CVAEs, including heart failure, hypertension, ischemia, and arrhythmia. Phase I studies may be underdetecting CVAEs. Future studies are needed to: identify patients at high-risk for CVAEs, develop optimal monitoring strategies, and explore therapies to mitigate these risks. [Table: see text]

Metabolic complications with the use of mTOR inhibitors for cancer therapy: A systematic review and meta-analysis.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 398-398 ◽  
Author(s):  
Shanthi Sivendran ◽  
Jian Ying ◽  
Benjamin Adam Gartrell ◽  
Neeraj Agarwal ◽  
Kenneth M. Boucher ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Incidence Rate ◽  
Meta Analysis ◽  
Mtor Inhibitors ◽  
Incidence Rates ◽  
Metabolic Complications ◽  
Randomized Controlled Clinical Trials ◽  
Grade 3

398 Background: mTOR inhibitors are approved in several malignancies including renal cell carcinoma (RCC). The risk of metabolic complications with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating temsirolimus, everolimus, and ridaforolimus in patients with all solid tumor malignancies. 16 eligible phase II clinical trials and 8 randomized controlled clinical trials were included in a systematic review and meta-analysis and the number of metabolic related AEs including hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were extracted. Incidence rates and incident rate ratios were calculated. Results: In total, 24 trials (including 4,261 patients) were included. The average incidence rate of any grade metabolic adverse events and grade 3-4 metabolic adverse events was 0.70 per patient and 0.11 (95% CI, 0.08, 0.15) per patient respectively. Analysis of the 3,317 patients across 8 RCT’s revealed that the log incidence rate ratio (IRR) of any grade metabolic adverse events with mTOR inhibitor therapy compared with control was 1.08 (95% CI, 0.84, 1.31) using a random-effects model. The risk of grade 3-4 adverse events was also increased with an IRR of 1.52 (95% CI, 1.05, 1.99). The IRR of all grade hyperglycemia was 1.08 (95% CI, 0.76, 1.40) and of grade 3-4 hyperglycemia was 1.66 (95% CI, 1.12, 2.20). The IRR of all grade hypertriglyceridemia was 0.91 (95% CI, 0.56, 1.26) and of grade 3-4 hypertriglyceridemia was 0.70 (95% CI,- 0.43, 1.83). The IRR of all grade hypercholesterolemia was 1.21 (95% CI, 0.77, 1.65) and of grade 3-4 hypercholesterolemia was 1.21 (95% CI, 0.77, 1.65). These findings suggest a statistically significant increase in the risk of hyperglycemia, hypercholesterolemia (all grades and grade 3 and 4), and all grade hypertriglyceridemia associated with mTOR therapy when compared with control. Conclusions: The risk of all grade and grade 3-4 metabolic adverse events are increased in patients treated with mTOR inhibitors compared with control. However, grade 3-4 metabolic adverse events remain relatively uncommon.

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

Vaccines ◽  
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.

scholarly journals Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3629
Author(s):  
Hsiao-Ling Chen ◽  
Yu-Kang Tu ◽  
Hsiu-Mei Chang ◽  
Tai-Huang Lee ◽  
Kuan-Li Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
Randomized Controlled ◽  
Extensive Stage ◽  
Grade 3

Patients with extensive-stage small cell lung cancer (ED-SCLC) have a very short survival time even if they receive standard cytotoxic chemotherapy with etoposide and platinum (EP). Several randomized controlled trials have shown that patients with ED-SCLC who received a combination of EP plus immune checkpoint inhibitors (ICIs) had superior survival compared with those who received EP alone. We conducted a systematic review and network meta-analysis to provide a ranking of ICIs for our primary endpoints in terms of overall survival (OS), progression free survival (PFS), and objective response rate (ORR), as well as our secondary endpoint in terms of adverse events. The fractional polynomial model was used to evaluate the adjusted hazard ratios for the survival indicators (OS and PFS). Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being best (Prbest) reference. EP plus nivolumab, atezolizumab or durvalumab had significant benefits compared with EP alone in terms of OS (Hazard Ratio HR = 0.67, 95% Confidence Interval CI = 0.46–0.98 for nivolumab, HR = 0.70, 95% CI = 0.54–0.91 for atezolizumab, HR = 0.73, 95% CI = 0.59–0.90 for durvalumab) but no significant differences were observed for pembrolizumab or ipilimumab. The probability of nivolumab being ranked first among all treatment arms was highest (SCURA = 78.7%, Prbest = 46.7%). All EP plus ICI combinations had a longer PFS compared with EP alone (HR = 0.65, 95% CI = 0.46–0.92 for nivolumab, HR = 0.77, 95% CI = 0.61–0.96 for atezolizumab, HR = 0.78, 95% CI = 0.65–0.94 for durvalumab, HR = 0.75, 95% CI = 0.61–0.92 for pembrolizumab), and nivolumab was ranked first in terms of PFS (SCURA = 85.0%, Prbest = 66.8%). In addition, nivolumab had the highest probability of grade 3–4 adverse events (SUCRA = 84.8%) in our study. We found that nivolumab had the best PFS and OS in all combinations of ICIs and EP, but nivolumab also had the highest probability of grade 3–4 adverse events in our network meta-analysis. Further head-to head large-scale phase III randomized controlled studies are needed to verify our conclusions.

Immune related adverse events (irAE) of mono-, combination, and sequential therapy regimens of ipilimumab (IPI), nivolumab (NIV), and pembrolizumab (PEM) for advanced melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21011-e21011
Author(s):  
Abdulaali Almutairi ◽  
Ali McBride ◽  
Srinath Sundararajan ◽  
Ivo Abraham
Keyword(s):  
Clinical Trials ◽  
Meta Analysis ◽  
Phase 1 ◽  
Random Effect ◽  
Sequential Therapy ◽  
Incidence Rates ◽  
Advanced Melanoma ◽  
Regulatory Agencies ◽  
Regulatory Documents ◽  
Grade 3

e21011 Background: The immunotherapy agents IPI, NIV, and PEM have transformed the management of advanced melanoma but are associated with irAEs. We estimated the incidence of irAEs as observed in clinical trials of mono, combination , and sequential regimens of these agents in the advanced melanoma setting. Methods: We searched the Medline, Embase, and Cochrane databases; clinicaltrials.gov; and websites of regulatory agencies in USA, Europe, Australia, and Japan for phase 1-3 trials of IPI, NIV, and PEM in advanced melanoma. Random effect meta-analysis was utilized to estimate the incidence of irAEs (expressed as % with 95%CI) for all agents in mono-, combination, and sequential regimens. Results: 56 reports (32 published articles, 7 updates, 15 results published on clinicaltrials.gov and 2 regulatory documents) of 37 trials and relating unique and independent irAE data were included in the analysis. See Table. Conclusions: IPI mono had higher incidence rates of all grade and ≥ grade 3 hypophysitis and colitis but lower rates of all grade hypothyroidism, pneumonitis, and vitiligo than NIV or PEM mono. Combination and sequential regimens had higher irAE incidence rates compared to monotherapies except for grade ≥3 hypophysitis in PEM+IPI and NIV→IPI, and grade ≥3 vitiligo as well as all grade colitis and hypophysitis in IPI →NIV. Table. Incidence rates of select irAEs expressed as % with 95%CI (‡ all grade; * ≥ grade 3). [Table: see text]

scholarly journals Recurrent TB: a systematic review and meta-analysis of the incidence rates and the proportions of relapses and reinfections

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215449
Author(s):  
Victor Vega ◽  
Sharon Rodríguez ◽  
Patrick Van der Stuyft ◽  
Carlos Seas ◽  
Larissa Otero
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Treatment Success ◽  
Drug Regimen ◽  
Incidence Rates ◽  
Recurrence Rates ◽  
Tb Treatment ◽  
Registration Number ◽  
Study Characteristics

BackgroundA recurrent tuberculosis (TB) episode results from exogenous reinfection or relapse after cure. The use of genotyping allows the distinction between both.MethodsWe did a systematic review and meta-analysis, using four databases to search for studies in English, French and Spanish published between 1 January 1980 and 30 September 2020 that assessed recurrences after TB treatment success and/or differentiated relapses from reinfections using genotyping. We calculated person years of follow-up and performed random-effects model meta-analysis for estimating pooled recurrent TB incidence rates and proportions of relapses and reinfections. We performed subgroup analyses by clinical–epidemiological factors and by methodological study characteristics.FindingsThe pooled recurrent TB incidence rate was 2.26 per 100 person years at risk (95% CI 1.87 to 2.73; 145 studies). Heterogeneity was high (I2=98%). Stratified pooled recurrence rates increased from 1.47 (95% CI 0.87 to 2.46) to 4.10 (95% CI 2.67 to 6.28) per 100 person years for studies conducted in low versus high TB incidence settings. Background HIV prevalence, treatment drug regimen, sample size and duration of follow-up contributed too. The pooled proportion of relapses was 70% (95% CI 63% to 77%; I²=85%; 48 studies). Heterogeneity was determined by background TB incidence, as demonstrated by pooled proportions of 83% (95% CI 75% to 89%) versus 59% (95% CI 42% to 74%) relapse for studies from settings with low versus high TB incidence, respectively.InterpretationThe risk of recurrent TB is substantial and relapse is consistently the most frequent form of recurrence. Notwithstanding, with increasing background TB incidence the proportion of reinfections increases and the predominance of relapses among recurrences decreases.PROSPERO registration numberCRD42018077867

scholarly journals Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis

PLoS Medicine ◽  
2021 ◽  
Vol 18 (9) ◽  
pp. e1003738
Author(s):  
Mercedes Yanes-Lane ◽  
Edgar Ortiz-Brizuela ◽  
Jonathon R. Campbell ◽  
Andrea Benedetti ◽  
Gavin Churchyard ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Preventive Therapy ◽  
Cochrane Library ◽  
People Living With Hiv ◽  
Drug Resistant ◽  
All Cause Mortality ◽  
Grade 3 ◽  
Living With Hiv

Background Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials. Methods and findings We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children. Conclusions Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.

DDRE-04. EFFECTIVENESS AND SAFETY OF OSIMERTINIB FOR PATIENTS WITH LEPTOMENINGEAL METASTASES FORM NON-SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi75-vi75
Author(s):  
Lei Wen ◽  
Changguo Shan ◽  
hui Wang ◽  
yanying Yang ◽  
Minting Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
Leptomeningeal Metastases ◽  
Small Cell Lung ◽  
Grade 3

Abstract BACKGROUND the FLAURA study established Osimertinib to be the priority choice for the treatment of metastatic non-small cell lung cancer (NSCLC) harboring mutated epidermal growth factor receptor (EGFR). However, like many previous studies, the FLAURA study excluded patients with symptomatic CNS metastases. Hence, we performed a systematic review and meta-analyses of studies to assess the efficiency and safety of Osimertinib for the treatment of NSCLC with leptomeningeal metastases (LM). METHODS We included studies published between 2010 and 2021 that evaluated the efficacy and toxicity of Osimertinib in NSCLC patients with LM. We searched PubMed, Embase, and oncology meeting abstracts (ASCO, ESMO and WCLC). Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate. We used the random-effects model to generate pooled estimates for proportions. Newcastle-Ottawa Scale (NOS) was used to assess the certainty in the evidence. RESULTS Twelve studies reporting on 367 patients were included in the meta-analysis. Most patients (≥90%) received Osimertinib as at least second line of treatment. The objective response rate was 42% (95% CI, 24%-59%; n = 184), and CNS disease control rate was 90% (95% CI, 85%-94%; n = 154). Intracranial progression free survival and overall survival ranged from 3.7 to 15.6 months, and 11.0 to 18.8 months, respectively. Adverse events were similar with previous studies and Common Terminology Criteria for Adverse Events (version 3.0) grade 3 or higher adverse event rates was acceptable. CONCLUSION This meta-analysis confirmed that for advanced NSCLC with LM harboring EGFR-TKI-sensitizing mutations, Osimertinib showed impressive antitumor activity and acceptable toxicity.

Sa1590 A Systematic Review and Meta-Analysis of Randomized Trials: Terlipressin Related Survival Benefit and Adverse Events in Treating Hepatorenal Syndrome

2016 ◽  
Vol 150 (4) ◽  
pp. S336
Author(s):  
Harsha Moole ◽  
Achuta Uppu ◽  
Raghuveer R. Boddireddy ◽  
Vishnu Moole ◽  
Sowmya Dharmapuri ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Survival Benefit ◽  
Randomized Trials ◽  
Hepatorenal Syndrome ◽  
Meta Analysis ◽  
Related Survival

scholarly journals Effects of dual blockade in heart failure and renal dysfunction: Systematic review and meta-analysis

2019 ◽  
Vol 20 (4) ◽  
pp. 147032031988265
Author(s):  
Alessandra Rodrigues Silva ◽  
Alexandre Goes Martini ◽  
Graziela De Luca Canto ◽  
Eliete Neves da Silva Guerra ◽  
Francisco de Assis Rocha Neves
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Adverse Events ◽  
Renal Dysfunction ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Renin Angiotensin System ◽  
Ras Inhibition ◽  
Increased Risk ◽  
Dual Blockade

Objective: The effect of dual renin–angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. Methods: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. Results: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 ( p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 ( p=0.0006) in all individuals, and to 0.86 ( p=0.005) in patients with RD and to 0.91 ( p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% ( p=0.00001). Conclusions: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.

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