391Gadobutrol enhanced CMR to detect significant coronary artery disease defined by quantitative coronary angiography. Results from two blinded phase III clinical trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Arai
Keyword(s):  
Diagnostic Accuracy ◽  
Meta Analysis ◽  
Significant Coronary Artery Disease ◽  
Quantitative Coronary Angiography ◽  
Phase Iii ◽  
Stress Perfusion ◽  
Cine Mri ◽  
Phase Iii Clinical Trials ◽  
Prior Literature ◽  
Minimum Performance

Abstract Background The FDA regulated GadaCAD1 trial and the nearly identical GadaCAD2 clinical trial aimed to determine whether gadobutrol-enhanced CMR can detect significant CAD. Methods Two multicenter, international trials enrolled patients with known or suspected CAD and used cine MRI, gadobutrol enhanced stress/rest perfusion, and late gadolinium enhancement. Endpoints, primary, and secondary minimum performance thresholds versus QCA and stress cine MRI are summarized in the table. There were 3 blinded, core-lab CMR readers per trial (6 readers overall) and 2 core-lab QCA readers. A meta-analysis combined results from all 6 CMR readers. Results 765 patients were analyzed (GadaCAD1: n=376, GadaCAD2: n=389). The meta-analysis of 6 readers had 79% sensitivity, 87% specificity, and AUC of 0.82 to detect a 70% QCA stenosis and met all study endpoints (figure & table). Versus a 50% QCA stenosis, the meta-analysis also met all study endpoints. At an individual reader level, all 6 readers met all study endpoints versus a 70% QCA stenosis. Versus a 50% QCA stenosis, only 1 of 6 readers exceeded the minimum performance threshold for sensitivity but all 6 readers met all other endpoints. For all readers, stress perfusion was more sensitive than stress wall motion (p<0.05). Diagnostic Accuracy Results Conclusions CMR stress perfusion has high diagnostic accuracy for significant CAD. The ROC analysis and overall results support prior literature that a 70% QCA threshold is a more appropriate threshold for physiologically significant CAD. Acknowledgement/Funding Bayer

Reno-vascular toxicities associated with carfilzomib: Systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21622-e21622
Author(s):  
Chintan Shah ◽  
Harini Bejjanki ◽  
Rohit Bishnoi ◽  
Ankur Jain ◽  
Subhankar Samal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Phase I ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Dose Effect ◽  
Phase Iii ◽  
Control Group ◽  
Phase Iii Clinical Trials

e21622 Background: Carfilzomib (Carf) is a novel proteasome inhibitor that is approved for patients with relapsed multiple myeloma (RMM) who have failed ≥ 1 prior lines of therapy. The incidence and seriousness of Carf associated reno-vascular toxicities (RVT) is not well known. We performed systematic review of Carf literature with meta-analysis to determine its incidence and overall risk. Methods: Initial search of literature led to a total of 175 Carf related articles. However, we used a total of 29 publications; phase I/II, phase II and phase III clinical trials (n = 3) which used Carf as monotherapy or in combination. We excluded phase I studies. Incidence rates and odds ratios (OR) were calculated with either fixed effect or random effect model based on the heterogeneity of included studies. Toxicity such as hypertension (HTN), renal failure (RF) and venous thromboembolism (VTE) were reported according to CTCAE v4.0. Results: A total of 4560 patients with various hematological and solid malignancies were included. Incidences of toxicities were: 15.9% and 4.7 % for HTN, 11.2% and 3.44% for RF, 6.47% and 2.22% for VTE, respectively for all grades and high grades in each category. When compared to control group taken from phase III clinical trials, the risk of HTN and RF due to Carf was significantly higher [OR = 2.91 and 3.32 in HTN (P < 0.001)], [OR = 1.71 and 1.79 (P < 0.05) for RF], respectively for all grade and high grade in each category. Moreover, incidence of HTN with higher than standard dose of carf (27 mg/m2 twice weekly) was significantly higher (P < 0.001). RF and VTE did not have the dose effect. Concomitant use of immunomodulator (IMiD) significantly increased, as expected, the incidence of VTE (P < 0.001). There was no variation in the incidence of RVT among newly diagnosed versus RMM (P = 0.4). Conclusions: Overall incidence and risk of hypertension and renal toxicities seems to be high when using Carf. Higher doses of Carf seem to lead to higher incidence of HTN, while the risk of VTE is higher with concomitant IMiD use. The pathophysiology for these complications is poorly understood, however it could be secondary to endothelial effect of carf. Physician should be vigilant about these effects as it can lead to poor overall outcomes.

The prognostic impact of KRAS mutation in colorectal cancer patients: A meta-analysis of phase III clinical trials.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e14515-e14515 ◽  
Author(s):  
Clarinda Wei Ling Chua ◽  
Dawn QQ Chong ◽  
Ravindran Kanesvaran ◽  
Wai Meng David Tai ◽  
Chee Kian Tham ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Meta Analysis ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Phase Iii Clinical Trials ◽  
Colorectal Cancer Patients

Apalutamide, darolutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer: a meta-analysis

2021 ◽  
Author(s):  
Mathieu Roumiguié ◽  
Xavier Paoletti ◽  
Yann Neuzillet ◽  
Romain Mathieu ◽  
Sebastien Vincendeau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Related Quality ◽  
Health Related

Aim: Comparison of the efficacy/safety/health-related quality of life of apalutamide, enzalutamide and darolutamide in Phase III clinical trials involving patients with nonmetastatic castration-resistant prostate cancer was performed. Materials & methods: Relevant studies were identified by searching PubMed as well as conference abstracts reporting updated overall survival. Three pivotal trials were identified, SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), and form the basis of this analysis. Results: All three drugs significantly prolonged metastasis-free survival, prostate-specific antigen response and overall survival versus placebo, and were generally well tolerated. Conclusion: Drug selection will likely be influenced by tolerability/safety and other factors, such as the propensity for drug–drug interactions and the presence of comorbidities, that affect the risk–benefit balance in individual patients.

Network Meta-analysis of Treatments for Chronic Plaque Psoriasis in Canada

2014 ◽  
Vol 18 (6) ◽  
pp. 371-378 ◽  
Author(s):  
Aditya K. Gupta ◽  
Deanne Daigle ◽  
Danika C.A. Lyons
Keyword(s):  
Clinical Trials ◽  
Plaque Psoriasis ◽  
Meta Analysis ◽  
Severity Index ◽  
Phase Iii ◽  
Chronic Plaque Psoriasis ◽  
Phase Iii Clinical Trials ◽  
Statistical Framework ◽  
Consistency Model ◽  
Systemic Treatments

Background: Psoriasis affects approximately 500,000 Canadians. Eight treatments are currently licensed for chronic plaque psoriasis in Canada. Objective: To compare the efficacy of systemic treatments for chronic plaque psoriasis for the outcome > 75% reduction in the Psoriasis Area and Severity Index (PASI) using network meta-analysis. Methods: PubMed and clinicaltrials.gov databases were searched up until October 15, 2013, for phase III clinical trials. A consistency model based on a random-effects bayesian statistical framework was used to compare the rates of > 75% PASI reduction across trials. Results: Twenty-one studies were included in the network analysis. Infliximab had significantly greater odds of producing > 75% reduction in the PASI compared to all treatments. All treatments conferred greater odds of > 75% PASI reduction compared to placebo. Conclusion: Although infliximab had the highest efficacy relative to other systemic treatments for psoriasis, adverse effects, cost, and patient preferences should also be considered when deciding on treatment.

scholarly journals Comparative Efficacy and Safety of Programmed Death-1 Pathway Inhibitors in Advanced Gastroesophageal Cancers: A Systematic Review and Network Meta-Analysis of Phase III Clinical Trials

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2614
Author(s):  
Laercio Lopes da Silva ◽  
Pedro Nazareth Aguiar ◽  
Robin Park ◽  
Eduardo Edelman Saul ◽  
Benjamin Haaland ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Success Rates ◽  
First Line ◽  
Phase Iii Clinical Trials ◽  
Third Line ◽  
Line Setting

Background: The use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 regimens with or without chemotherapy; Methods: We performed a network meta-analysis (NMA) of anti-PD-1/PD-L1 monotherapy or combined with chemotherapy (chemoimmunotherapy) for gastroesophageal cancers without ERBB2 overexpression; Results: The first-line NMA included four trials (N = 3817), showing that chemoimmunotherapy improved OS and PFS without significant safety difference: Nivolumab-chemotherapy, OS (HR: 0.83 [95% CI, 0.75–0.92]), PFS (HR 0.68 [95% CI, 0.57–0.81]), Pembrolizumab-chemotherapy: OS (HR 0.77 [95% CI, 0.67–0.88]), PFS (HR: 0.72 [95% CI, 0.60–0.85]. Pembrolizumab monotherapy was the safest first-line treatment, SAE (OR 0.02 [95% CI, 0.00–0.2]) but showed no survival benefit. The second-line NMA encompassed four trials (N = 2087), showing that anti-PD-1 significantly improved safety but not survival: camrelizumab, SAE (OR 0.37; [95% CI, 0.24–0.56]); nivolumab, SAE (OR 0.13, [95% CI, 0.08–0.2]) pembrolizumab, SAE (OR 0.4; [95% CI, 0.30–0.53]); Conclusions: chemoimmunotherapy improves OS and PFS in previously untreated gastroesophageal cancers. Anti-PD-1 monotherapies improve safety in refractory disease, with no significant survival benefit.

Efficacy and toxicity of CDK 4/6 inhibitors in breast cancer: Systematic review and meta-analysis of the phase III clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14591-e14591 ◽  
Author(s):  
Faheem Farooq ◽  
Jules A. Cohen
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Meta Analysis ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Cochrane Library ◽  
Line Treatment ◽  
Treatment Trials ◽  
Phase Iii Clinical Trials ◽  
Grade 3

e14591 Background: Selective CDK4/6 inhibitors such as palbociclib, abemaciclib, and ribociclib have demonstrated efficacy in advanced HR+/HER2- breast cancer. Drug-related toxicity has been manageable, but variable amongst the drugs. This meta-analysis was conducted to guide CDK inhibitor choice based on efficacy and toxicity. Methods: A systematic literature review of Pubmed, Cochrane Library, and EMBASE was performed in December 2018. Efficacy was evaluated via reported progression free survival (PFS) and pooled hazard ratios (HR). Overall response rate (ORR), treatment discontinuation, and treatment-related adverse events (AEs) were measured via pooled odds ratios (OR). Meta-analyses were performed using random effects modeling and 95% confidence intervals (CI). Results: A pooled analysis of 7 phase III clinical trials (n = 4415) demonstrated a HR of 0.55 (CI: 0.51-0.60) for PFS and an OR of 1.93 (CI: 1.54-2.42) for ORR. First-line treatment trials (n = 3020) pairing CDK 4/6 inhibitors with NSAI/tamoxifen had a HR of 0.56 (CI: 0.51-0.60) for prolonged PFS and an OR of 1.64 (CI: 1.39-1.95) for ORR. Second-line treatment trials (n = 1916) pairing CDK 4/6 inhibitors with fulvestrant had an HR of 0.54 (CI: 0.48-0.61) for prolonged PFS and an OR of 2.48 (CI: 1.57-3.90) for ORR. Palbociclib and ribociclib had similar rates of grade 3/4 AEs, neutropenia, and treatment discontinuation. Abemaciclib had lower rates of grade 3/4 AEs overall, but significantly increased rates of diarrhea and treatment discontinuation due to AEs. Conclusions: Each drug demonstrated a significant improvement in PFS. However, there is no statistical difference in efficacy among the three CDK inhibitors. Treatment decisions can be guided by the tolerability of AEs amongst the medications. Further patient follow-up will illuminate whether there is an OS advantage in this novel drug class. [Table: see text]

Safety of Low-Dose Tanezumab in the Treatment of Hip or Knee Osteoarthritis: A Systemic Review and Meta-analysis of Randomized Phase III Clinical Trials

Pain Medicine ◽  
2020 ◽  
Author(s):  
Yang Yu ◽  
Shi-Tao Lu ◽  
Jin-Peng Sun ◽  
Wei Zhou
Keyword(s):  
Low Dose ◽  
Total Joint Replacement ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Optimal Dose ◽  
Phase Iii ◽  
Systemic Review ◽  
Phase Iii Clinical Trials ◽  
Relative Risks ◽  
Significant Difference

Abstract Objectives To evaluate the safety of low-dose tanezumab in the treatment of knee or hip osteoarthritis (OA). Methods Databases were searched up to September 2019 for phase III randomized controlled trials (RCTs). Eleven phase III RCTs comprising 11,455 patients were eligible. The pooled estimates of safety outcomes were assessed and expressed using relative risks (RRs) and 95% confidence intervals with a random-effects model. Results Tanezumab significantly increased the incidence of rapidly progressive OA (RPOA; RR = 9.07, 95% CI = 1.21–67.90, P = 0.03) and abnormal peripheral sensation (APS; RR = 2.68, 95% CI = 1.64–4.37, P &lt; 0.00001) compared with placebo. No significant difference was found in terms of incidence of total joint replacement (TJR; RR = 1.13, 95% CI = 0.76–1.68, P = 0.55) or withdrawal due to adverse effects (AEs; RR = 1.26, 95% CI = 0.79–2.00, P = 0.33). The tanezumab group showed a statistically higher incidence of RPOA (RR = 3.96, 95% CI = 2.23–7.04, P &lt; 0.00001) and APS (RR = 1.2, 95% CI = 1.44–2.56, P &lt; 0.00001) compared with the nonsteroidal anti-inflammatory drugs and opioids group. No significant difference was found in terms of TJR (RR = 1.51, 95% CI = 0.65–3.47, P = 0.33) and withdrawal (RR = 0.54, 95% CI = 0.20–1.40, P = 0.20). Subgroup analysis revealed that 2.5 mg of tanezumab did not show an advantage over 5 mg of tanezumab in reducing AEs. Conclusions These results demonstrate that RPOA and APS should be the most concerning AEs when using tanezumab in OA patients. Additional data are needed to define the optimal dose to minimize risk and to determine the optimal subjects to receive this treatment.

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.

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