Improving tolerability of pembrolizumab with weight based dosing: A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2639-2639
Author(s):  
Nabeela Khan Patail ◽  
Amna Falak Sher ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Placebo Control ◽  
Clinical Activity ◽  
Discontinuation Rate ◽  
Random Effects Models ◽  
American Society ◽  
The Impact

2639 Background: Pembrolizumab, a PD-1 immune checkpoint inhibitor (ICI), has demonstrated significant clinical activity in various cancers. Despite a favorable toxicity profile, discontinuation due to adverse events including immune related adverse events (irAE) has been reported. We conducted a meta-analysis of published clinical trials to evaluate the tolerability of pembrolizumab in cancer patients. Methods: A systematic review was conducted of relevant studies from the databases of PubMed and abstracts presented at American Society of Clinical Oncology (ASCO) from June 2015 until September 2020. Eligible studies included prospective clinical trials that reported a discontinuation rate due to adverse effects. Incidence, relative risk and 95% confidence intervals (CI) were calculated by employing fixed or random effects models. Results: A total of 6,380 patients with a variety of hematologic and solid malignancies from 20 studies of pembrolizumab were included for analysis. The overall rate of pembrolizumab discontinuation due to adverse events was 8.2% (95% CI: 6.4-10.4%). The discontinuation rate of pembrolizumab was not significantly lower than the chemotherapy controls, with RR of 0.84 (95% CI: 0.58-1.12, p = 0.33). However, the discontinuation rate of pembrolizumab was significantly higher compared to placebo control with RR of 2.20 (95% CI: 1.36-3.54, p < 0.001), and significantly lower compared to ipilimumab with RR of 0.58 (95% CI: 0.34-0.99, p = 0.04) respectively. The discontinuation rate varied widely among different tumor types with the lowest rate of 0.8% (95% CI: 0.2-3%) in gastric cancer, and the highest of 13.5% (95% CI: 10.8-16.8%) in head and neck squamous cell carcinoma. Interestingly, the discontinuation rate varied with pembrolizumab dosing, with the fixed dosing of 200mg being 9.2% (95% CI: 6.9-12%) and the weight-based dosing being 6.5% (95% CI: 4.8-8.8%). The weight-based dosing was associated with a significantly lower discontinuation rate compared to controls with RR of 0.62 (95% CI: 0.47-0.81, p < 0.0001), while the fixed dosing had similar discontinuation rate with RR of 1.03 (95% CI: 0.89-1.20, p = 0.67). Conclusions: The tolerability of pembrolizumab may be comparable to chemotherapy in cancer patients and may vary with its dosing. Future studies are warranted to evaluate the impact of different dosing.

Fatal adverse events associated with pembrolizumab in cancer patients: A meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2561-2561
Author(s):  
Gol Minoo Golshani ◽  
Amna Falak Sher ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Random Effects Models ◽  
Programmed Cell Death 1 ◽  
Significant Difference ◽  
American Society ◽  
Fatal Adverse Events ◽  
Tumor Types

2561 Background: Pembrolizumab, an immune checkpoint inhibitor (ICI) against programmed cell death-1(PD-1) protein has emerged as an effective treatment for many cancers. Although better tolerated than chemotherapy, it has unique immune related adverse event and little is known about its risk of fatal adverse events (FAE). Therefore, we conducted a meta-analysis of clinical trials to determine the incidence and risk of fatal adverse events with pembrolizumab. Methods: A systematic search for phase I-III clinical trials of pembrolizumab was conducted using databases from PUBMED, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October 2018. Eligible studies included prospective clinical trials of pembrolizumab with available data on FAE. Data on FAE was extracted from each study and pooled for calculations. Incidence, relative risk (RR) and 95% confidence intervals (CI) were calculated by employing fixed or random-effects models. Results: A total of 11 clinical trials of pembrolizumab, with 3713 patients were included for analysis. The overall incidence of FAE with pembrolizumab was 1.2% (95% CI: 0.5-2.8%).The incidence of FAE significantly varied among different tumor types (P=0.02), ranging from 0.2% in melanoma to 3.1% in breast cancer.The incidence of FAE was significantly higher (P<0.001) with chemotherapy plus pembrolizumab (7.0%, 95%CI: 4.9-10%) as compared to pembrolizumab alone (0.7%, 95% CI: 0.4-1.2, p=<0.001). There was no significant difference in the risk of FAEs when pembrolizumab was compared with chemotherapy with RR=1.24 (95% CI: 0.8-1.89, P=0.31). Conclusions: Pembrolizumab is similar to chemotherapy in the risk of fatal adverse events in cancer patients. Combination of pembrolizumab with chemotherapy increased the risk of FAE in comparison with pembrolizumab alone. Further studies are needed to identify risk factors. [Table: see text]

Tolerability of single agent nivolumab in cancer patients—A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15146-e15146
Author(s):  
Judy Huang ◽  
Alejandro Ramon Carvajal ◽  
Shenhong Wu
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitor ◽  
Meta Analysis ◽  
Single Agent ◽  
Fixed Dose ◽  
Discontinuation Rate ◽  
Relative Risks ◽  
Immune Mediated ◽  
American Society

e15146 Background: Nivolumab, a PD-1 immune checkpoint inhibitor, is being widely utilized in a number of cancers as a single agent. Adverse events, including those that are immune mediated, have been reported that resulted in discontinuation of the drug. We conducted a meta-analysis of published clinical trials to further investigate the tolerability of nivolumab in cancer patients. Methods: Databases, including PubMed and abstracts presented at American Society of Clinical Oncology annual meetings from 2015 to December 2019 were searched to identify relevant studies. This included randomized controlled trials and single arm trials that reported a discontinuation rate due to adverse events. Incidences and relative risks were calculated based on the heterogeneity of included studies. Results: Seventeen studies published between 2015 and 2019 were selected, which included a total of 4216 patients. Overall, the discontinuation rate of nivolumab due to adverse events was 6.7% (95% CI 4.7-9.5%). The rate varied significantly with the type of cancer (p < 0.001). The lowest discontinuation rate was in NSCLC of 2.1% (95% CI 1.3-2.3%), and the highest discontinuation rate was in melanoma of 15.2% (95% CI 6.8-30.6%). In addition, significantly higher intolerability is associated with the fixed dose of nivolumab at 240 mg than 3 mg/kg (P = 0.004). In comparison with chemotherapy controls, the intolerability in the nivolumab group was not significantly different, with a relative risk of 0.97 (95% CI: 0.36-2.6). Conclusions: The intolerability of nivolumab as monotherapy may be similar to chemotherapy, and can be improved with dose adjustment.

Tolerability of dual checkpoint blockade with nivolumab and ipilimumab: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15149-e15149
Author(s):  
Alejandro Ramon Carvajal ◽  
Judy Huang ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Risk Mitigation ◽  
Meta Analysis ◽  
Checkpoint Blockade ◽  
Discontinuation Rate ◽  
Fixed Effects Model ◽  
Increased Risk

e15149 Background: The dual checkpoint blockade of PD-1 and CTLA-4 with nivolumab and ipilimumab have been used extensively for cancer immunotherapy in clinical practice and trials due to its efficacy. A critical concern is the tolerability of the combination due to the increased risk of severe immune-mediated adverse events. A meta-analysis of clinical trials was performed to assess the treatment tolerability measured as discontinuation due to adverse events. Methods: A search through PubMed as well as abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until December 2019 was performed to identify clinical trials in which the combination of nivolumab and ipilimumab was given to cancer patients. Eligible clinical trials reported a discontinuation rate due to adverse events for the groups of patients receiving nivolumab and ipilimumab. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals. Results: Seven clinical studies which included a total of 3,213 patients (combo: 1746, control: 1467) with various cancers were selected. Overall, the intolerability of nivolumab and ipilimumab measured as the summary incidence of discontinuation due to adverse events was 25.1% (95% CI: 17.8-34.1%). The rate varied significantly with the type of cancer (P < 0.001). The lowest discontinuation rate was in uveal melanoma, with a rate of 11% (95% CI: 2.9-34.2%), and the highest discontinuation rate was in melanoma at 46.3% (95% CI: 36.6-56.4%). In comparison with chemotherapy controls from randomized controls, the intolerability was significantly higher with an relative risk of 2.1 (95% CI: 1.78-2.84) for the combination. Conclusions: There is a substantial risk for intolerability in cancer patients receiving the combination nivolumab and ipilimumab. Further studies are needed for risk mitigation.

Hemorrhagic and thrombotic events in oncology patients treated with antiangiogenic therapy: Impact of study design on the results assessed by meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14058-e14058
Author(s):  
Jane-Chloe Trone ◽  
Céline Chapelle ◽  
Edouard Ollier ◽  
Laurent Bertoletti ◽  
Michel Cucherat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Study Design ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Antiangiogenic Therapy ◽  
Solid Cancer ◽  
Increasing Risk ◽  
Meta Analyses ◽  
The Impact

e14058 Background: Antiangiogenic (AA) therapies emerge as a new cornerstone for cancer treatment, but carry their own particular risk profile. Several previous meta-analyses have showed increasing risk of bleeding and paradoxically thrombosis in cancer patients receiving antiangiogenic. The aim of the meta-analysis is to investigate the impact of studies design (open or double blind (DB)), on the incidence and the occurrence of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated by AA therapies. Methods: We searched Medline, Cochrane, ClinicalTrial databases, meeting abstracts of the American Society of Clinical Oncology and the European Society of Medical Oncology for relevant clinical trials. We included prospective phase II and III clinical trials that randomly assigned patients with solid cancer to AA therapy or control. Statistical analyses were conducted to calculate the summary incidence, ORs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 166 trials (72,024 patients) were included. For bleeding events, comparison on AA treatment versus control yielded an OR of 2.41 (95% CI 2.07 to 2.71; p < 0.001) with an exaggeration of treatment effects by 68% (95% CI, 33 to 113) in open-label studies compared with DB trials. Concerning VTE, an OR of 1.18 (95% CI 1.04 to 1.35; p = 0.0115) was noted, with a significant enhancement of 53% (95% CI, 19 to 96) of treatment side effects with open trials compared with DB trials. AA don’t increase significantly the frequency of VTE when considering only DB trials. For ATE, an OR of 1.59 (95% CI 1.30 to 1.94; p < 0.001) was observed, associated with a significant exaggeration of 65% (95% CI, 13 to 143) with open trials compared with DB trials. Conclusions: The present meta-analysis showed a significant interaction of study design for the tolerance assessment in the AA therapies in cancers. The increasing risk of hemorrhagic events, VTE and ATE appear to have been overestimated in the previous meta-analyses. In the future, meta-analyses should be restricted to DB trials for analysis of toxicity profile.

Erythropoiesis Stimulating Agent (ESA) Use for Anemic Cancer and Chronic Kidney Disease (CKD) Patients in 2008: Advocacy for Conservative Use

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4680-4680
Author(s):  
Charles L. Bennett ◽  
Benjamin Kim ◽  
Athena T Samaras ◽  
Allen R Nissenson ◽  
A. Oliver Sartor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Kidney Disease ◽  
Cancer Patients ◽  
Basic Science ◽  
Meta Analysis ◽  
Cardiovascular Risks ◽  
Increased Risk ◽  
American Society ◽  
Meta Analyses ◽  
Patient At Risk

Abstract The ESAs epoetin and darbepoetin were approved for treatment of chemotherapy-associated anemia in 1993 and 2002 and CKD-associated anemia in 1989 and 2001, respectively. In 2006, ESAs were the largest single pharmaceutical expenditure by the Center for Medicare and Medicaid Studies (CMS). Recently, a series of preclinical experiments, clinical trials, and meta-analyses of ESAs have been reported. The Food and Drug Administration (FDA), National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH)/American Society of Clinical Oncology (ASCO), and Kidney Disease Outcomes Quality Improvement (KDOQI) have issued guideline statements for ESAs, and CMS has implemented an ESA Monitoring Policy (EMP) to help ensure appropriate ESA claims. Herein, we analyze these actions and usage trends of ESAs for anemic cancer and CKD patients. Data sources included basic science studies, clinical trials, meta-analyses, notifications from CMS, ESA manufacturers, and the FDA, guidelines from the NCCN, ASH/ASCO, and KDOQI, and published reports regarding ESA usage reported between 2006 and 2008. Search terms included erythropoietin, darbepoetin, anemia, neoplasm, and CKD. Results from eight recent clinical trials and one 2008 meta-analysis for anemic cancer patients identified tumor progression and mortality risks with ESA versus placebo/control use. Analyses from one clinical trial and one 2008 meta-analysis for CKD patients identified mortality and cardiovascular risks when high hemoglobin levels were targeted. Guidelines, manufacturer notifications, and reimbursement policies have become increasingly conservative. ESA administration to anemic cancer and CKD patients has decreased. Among anemic cancer patients, red blood cell transfusions are increasing and ESA use is decreasing. Among anemic CKD patients, target and achieved hemoglobin levels and ESA doses have decreased. Regulatory, clinical and professional communities now advocate for conservative use of ESAs for anemic patients with cancer or CKD. Chemotherapy-associated anemia CKD-associated anemia Basic Science ESAs may be harmful: Erythropoietin receptors have been identified in tumor cells and have demonstrated downstream cellular effects including proliferation, anti-apoptosis, invasion, and chemotherapy resistance. ESAs may be beneficial: Studies have identified neurotrophic and neuroprotective effects of erythropoietin. Also, erythropoietin protects against hypoxia-induced apoptosis, ischemia-reperfusion injury, and promotes ventricular modeling. Clinical Trials and Meta-analyses Eight clinical trials and one meta-analysis have identified increased risk of mortality and/or tumor progression associated with ESA use. Two meta-analyses have identified significantly increased risk of VTE and seven trials reported four-fold or greater increased risk of VTE. One trial and one meta-analysis have identified mortality and cardiovascular risks when ESAs were targeted to higher versus lower hemoglobin levels. A second trial did not identify clinical benefits with ESA administration targeted to normal versus lower hemoglobin levels. Guidelines NCCN and ASH/ASCO guidelines support ESA administration targeted to between 10 and 12 g/dl and a trigger hemoglobin level to initiate ESA use at 10 g/dl. KDOQI supports hemoglobin levels targeted to between 11 and 12 g/dl and avoiding levels &gt; 13 g/dl. Recent Manufacturer Notifications The FDA mandated that product labels state that ESAs are not indicated for patients receiving myelosuppressive therapy with curative intent, the trigger hemoglobin should be &lt;10 g/dl, and ESAs should be withheld if the hemoglobin exceeds a level necessary to avoid transfusion. Revised labels indicated hemoglobin levels should be targeted to between 10 and 12 g/dl and that high ESA doses should be avoided. Reimbursement Policies Target and trigger hemoglobin levels of &lt; 10 g/dl and a maximum duration of 8 weeks of treatment are supported by CMS. Target hemoglobin levels &lt; 13 g/dl are supported by CMS. Reimbursement is reduced when hemoglobin levels &gt; 13 g/dl are recorded for 3 or more consecutive billing cycles. Usage Trend Between November 2006 and October 2007, usage of ESAs declined from 42% to 15% per patient at risk while transfusions increased from 24% to 28% per patient at risk. ESA use among CKD patients not on hemodialysis decreased from 54% to 42% from 2007 to 2008.

Risk of pneumonitis with mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13573-e13573
Author(s):  
Vishal Navnitray Ranpura ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Cancer Therapeutics ◽  
Mtor Inhibitors ◽  
High Grade ◽  
Significant Difference ◽  
American Society

e13573 Background: Pneumonitis is associated with the use of mTOR inhibitors, everolimus and temsirolimus, which have been used widely in cancer therapeutics and clinical trials. Currently, the overall risk of pneumonits in patients treated with mTOR inhibitors has not been defined. We performed a systematic review and meta-analysis of published clinical trials to assess the risk of pneumonitis in cancer patients treated with mTOR inhibitors. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences until May 2012 were searched to identify relevant studies. Eligible studies included prospective clinical trials in which patients received treatment with everolimus or temsirolimus as a single agent or in combination with other agents. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated employing a fixed- or random-effects model based upon the heterogeneity of the included studies. Results: A total of 2,303 patients with a variety of tumors from 18 studies (everolimus: 12, temsirolimus: 6) were included for the analysis. The overall incidences of all-grade and high-grade pneumonitis with mTOR inhibitors were 6.5% (95% CI: 3.7-11.1%) and 2.5% (95% CI 1.2-5.4%) respectively. The risk of all-grade pneumonitis did not vary significantly with tumor types (P=0.079), but vary significantly with their combination with other agents (P<0.001). There was no significant difference between everolimus and temsirolimus in the incidence of all-grade (P=0.22) and high-grade (P=0.28) pneumonitis. In comparison with controls, mTOR inhibitors significantly increased the risk of all-grade (RR=5.2, 95% CI: 2.09-12.93, P<0.001) but not high-grade pneumonits (RR=2.63, 95% CI: 0.66-10.40, P=0.41). Conclusions: The risk of pneumonitis is increased in cancer patients receiving mTOR inhibitors without significant difference between everolimus and temsirolimus.

Risk of proteinuria with the new angiogenesis inhibitor axitinib in patients with cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20602-e20602
Author(s):  
Andrew Kuei ◽  
Xiaolei Zhu ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Significant Risk ◽  
Angiogenesis Inhibitor ◽  
Growth Factor Receptor ◽  
High Grade ◽  
Random Effects Models ◽  
Treatment Interruptions ◽  
Significant Difference

e20602 Background: The use of axitinib, a potent inhibitor of vascular endothelial growth factor receptor (VEGFR), is associated with proteinuria, which may cause morbidity and treatment interruptions in cancer patients. We performed a systematic review and meta-analysis of published clinical trials to assess the overall risk of proteinuria with axitinib. Methods: Potentially relevant studies were identified by searching databases including Pubmed and abstracts presented at the American Society of Clinical Oncology annual meetings until June, 2012. Eligible studies included prospective clinical trials in cancer patients treated with axitinib containing data on proteinuria. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated using the fixed- or random-effects models. Results: A total of 1,671 patients with advanced renal cell carcinoma (RCC) and other solid tumors from 9 studies were included for analysis. The overall incidences of all-grade and high-grade (grade 3 or 4) proteinuria with axitinib were 22.7% (95% CI: 10.4-42.6%) and 3.8% (95% CI: 2.6-5.7%) respectively. The risk did not vary significantly with tumor types (P=0.13). There was no significant difference between RCC and non-RCC patients (P=0.45), although the incidence in RCC patients was higher (30.0%, 95% CI: 8.4-66.7 versus 17.5%, 95% CI: 7.4-36.3%). In comparison with a control (gemcitabine), axitinib significantly increased the incidence of high-grade proteinuria (3.3%, 95% CI: 1.6-6.5% versus 0.1%, 95% CI: 0-2.3%; P=0.031). When compared to another angiogenesis inhibitor sorafenib, axitinib did not have a significantly higher risk of all-grade (RR=1.48, 95% CI: 0.92-2.38, P=0.10) and high-grade proteinuria (RR=1.81, 95% CI: 0.68-4.85, P=0.24). Conclusions: There was a significant risk of proteinuria associated with the use of axitinib in cancer patients.

scholarly journals P01.06 Overweight and obesity as biomarkers for survival outcomes and immune related adverse events undergoing immunotherapy – a systematic review and meta-analysis

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A5.2-A6
Author(s):  
P Trinkner ◽  
S Günther ◽  
M von Bergwelt ◽  
D Cordas dos Santos ◽  
S Theurich
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Obese Patients ◽  
Increased Risk ◽  
Underweight Patients ◽  
The Impact

BackgroundThe impact of overweight/obesity in cancer patients treated with immune checkpoint inhibitors (ICIs) is controversial. To further contribute to this debate, we performed a systematic review and meta-analysis of published articles evaluating the effects of overweight/obesity on survival and immune-related adverse events (irAEs).Materials and MethodsIn analogy to Cochrane recommendations, systematic literature searches included all published articles in PubMed until February 2021 with key terms ‘obesity’ and ‘overweight’ and ICI treatment irrespective of cancer entity and ICI used. Further selection criteria for meta-analysis included WHO cut-offs for overweight/obesity. For the random effects meta-analysis, we used Hazard Ratios (HR) for overall and progression-free survival (OS, PFS) and Odds Ratios (OR) for occurrence of irAEs with corresponding 95% confidence intervals (95%CI), respectively.ResultsA total of 30 studies (12,895 patients, 38% female) selected for meta-analysis revealed a superior survival of overweight/obese patients (PFS: HR 0.9, 95%CI 0.77-1.04, p = 0.11; OS: 0.74, 95%CI 0.63-0.92, p = 0.0005) compared to normal weight patients. In subgroup analyses based on sex, overweight/obese male patients showed increased survival (PFS: HR 0.79, 95%CI 0.63-1.00, p = 0.05; OS: 0.71, 95%CI 0.58-0.86, p = 0.0005), whereas overweight/obese female patients had similar survival probabilities compared to their normal weight counterparts (PFS: HR 1.01, 95%CI 0.69-1.47, p = 0.96; OS: HR 0.73, 95%CI 0.48-1.10, p = 0.13). Underweight patients showed inferior survival (PFS: HR 1.48, 95%CI 1.07-2.04, p = 0.02; OS: HR 1.86, 95%CI 1.13-3.04, p = 0.01). In addition, overweight/obese patients had a higher risk of developing irAEs with grade ≥ 3 (OR 1.91, 95%CI 1.18-3.10, p = 0.008).ConclusionsOur meta-analysis revealed that overweight/obesity is a beneficial factor for PFS and OS in a mixed cohort of cancer patients undergoing ICI treatment accompanied by an increased risk of severe irAEs. The differences between overweight/obese males and overweight/obese females might point to sex specific adipose distribution patterns and interactions of sex steroids on a molecular level. A significant number of studies included underweight patients into normal weight control groups which led to a compromised interpretation of the data and should be addressed in future studies.Disclosure InformationP. Trinkner: None. S. Günther: None. M. von Bergwelt: None. D. Cordas dos Santos: None. S. Theurich: None.

scholarly journals Efficacy and Safety of COVID-19 Vaccines in Phase III Trials: A Meta-Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 582
Author(s):  
Haoyue Cheng ◽  
Zhicheng Peng ◽  
Wenliang Luo ◽  
Shuting Si ◽  
Minjia Mo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Meta Analysis ◽  
Phase Iii ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Common People ◽  
Random Effects Models ◽  
Phase Iii Clinical Trials ◽  
Phase Iii Trials

Nowadays, the vaccination with COVID-19 vaccines is being promoted worldwide, professionals and common people are very concerned about the efficacy and safety of COVID-19 vaccines. No published systematic review and meta-analysis has assessed the efficacy and safety of the COVID-19 vaccines based on data from phase III clinical trials. Therefore, this study has estimated the efficacy and safety of COVID-19 vaccines and the differences between vaccine types. PubMed, Embase, the Cochrane Library, CNKI, Wanfang, medRxiv databases and two websites were used to retrieve the studies. Random-effects models were used to estimate the pooled efficacy and safety with risk ratio (RR). A total of eight studies, seven COVID-19 vaccines and 158,204 subjects were included in the meta-analysis. All the vaccines had a good preventive effect on COVID-19 (RR = 0.17, 95% CI: 0.09–0.32), and the mRNA vaccine (RR = 0.05, 95% CI: 0.03–0.09) was the most effective against COVID-19, while the inactivated vaccine (RR = 0.32, 95% CI: 0.19–0.54) was the least. In terms of safety, the risk of overall adverse events showed an increase in the vaccine group after the first (RR = 1.46, 95% CI: 1.03–2.05) or second (RR = 1.52, 95% CI: 1.04–2.20) injection. However, compared with the first injection, the risk of local (RR = 2.64, 95% CI: 1.02–6.83 vs. RR = 2.25, 95% CI: 0.52–9.75) and systemic (RR = 1.33, 95% CI: 1.21–1.46 vs. RR = 1.59, 95% CI: 0.84–3.01) adverse events decreased after the second injection. As for the mRNA vaccine, the risk of overall adverse events increased significantly, compared with the placebo, no matter whether it was the first (RR = 1.83, 95% CI = 1.80–1.86) or the second (RR = 2.16, 95% CI = 2.11–2.20) injection. All the COVID-19 vaccines that have published the data of phase III clinical trials have excellent efficacy, and the risk of adverse events is acceptable. The mRNA vaccines were the most effective against COVID-19, meanwhile the risk and grade of adverse events was minimal, compared to that of severe symptoms induced by COVID-19.

Tolerability of axitinib in advanced renal cell carcinoma: A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16536-e16536
Author(s):  
Bareia Chaudhry ◽  
Shenhong Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Single Agent ◽  
Advanced Renal Cell Carcinoma ◽  
Discontinuation Rate

e16536 Background: Axitinib has been used extensively as a single agent or in combination with immunotherapy in the treatment of advanced renal cell carcinoma. It can be often discontinued due to adverse events. A meta-analysis of clinical trials was performed to evaluate the overall tolerability of axitinib in this setting. Methods: PubMed (Up to November 2020) was searched to identify clinical trials of axitinib in advanced or metastatic renal cell carcinoma. Reported data was collected to include axitinib and control discontinuation due to adverse events. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals depending on the heterogeneity of included studies. Results: A total of 11 studies including 4,056 patients (axitinib alone n = 1384, axitinib combination n = 987, control n = 1685) were included for analysis. The summary discontinuation rate for axitinib due to adverse events was 13.4% (95% CI; 11.7-15.2%) with 8.9% (95% CI: 5.3-14.6%) as a single agent and 26.6% (95% CI:17.8 –37.8%) in combination with other agents. In comparison with controls based on randomized controlled studies, axitinib overall has similar discontinuation rate due to adverse events (RR: 1.18, 95% CI: 0.77-1.80). However, there was a significantly higher discontinuation rate with axitinib in combination with other agents including immunotherapeutic agents PD-L1 inhibitors than control treatment (RR: 1.52, 95% CI: 1.24-1.86). Conclusions: The tolerability of axitinib may vary significantly with its use as a single agent or in combination in the treatment of advanced renal cell carcinoma. Further studies are needed to improve its tolerability as a part of combination therapy.

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