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Safety and efficacy of atezolizumab in the treatment of cancers: a systematic review and pooled-analysis.

ABSTRACT: Purpose:Immune checkpoint inhibitors have developed rapidly and have demonstrated antitumor activity in various cancers. To evaluate the safety and efficacy of atezolizumab in treating cancers, we conducted this meta-analysis. Methods:Embase, PubMed, MEDLINE, the Central Register of Controlled Trials of the Cochrane Library, and the American Society of Clinical Oncology database were searched for relevant studies. The primary outcomes were any grade adverse events (AEs) and grade ?3 AEs. The secondary outcomes were overall objective response rate, pooled 6-month progression-free survival (PFS) rate, 1-year overall survival (OS) rate, median PFS, and median OS. Results:Our meta-analysis was based on 14 clinical trials with 3,266 patients. The total risk of any grade AEs reached 69%, while grade ?3 AEs happened in only 13% of participants. The overall atezolizumab-related death rate was 0.17%. Major common AEs involved fatigue (24.5%), decreased appetite (13.2%), nausea (12.3%), diarrhea (10.8%), pyrexia (10.7%), pruritus (9.6%), cough (9.5%), edema peripheral (8.6%), and rash (8.4%). The most common severe AEs were fatigue (2.2%), anemia (1.9%), and dyspnea (1.9%). Meanwhile, we found that 6% patients reached complete response and 16% partial response. The pooled 6-month PFS rate and 1-year OS rate were 0.36 (95% CI: 0.31-0.41) and 0.55 (95% CI: 0.49-0.61), respectively. The median PFS varied from 1.5 to 6.1 months, and the median OS ranged from 5.9 to 28.9 months. Conclusion:Atezolizumab has a considerable potential in treating cancers with an acceptable risk profile.

SUBMITTER: Tie Y

PROVIDER: S-EPMC6366347 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Safety and efficacy of atezolizumab in the treatment of cancers: a systematic review and pooled-analysis.

Tie Yan Y Yang Hui H Zhao Rui R Zheng Heng H Yang Daoke D Zhao Jingyi J Liu Ming M

Drug design, development and therapy 20190204

<h4>Purpose</h4>Immune checkpoint inhibitors have developed rapidly and have demonstrated antitumor activity in various cancers. To evaluate the safety and efficacy of atezolizumab in treating cancers, we conducted this meta-analysis.<h4>Methods</h4>Embase, PubMed, MEDLINE, the Central Register of Controlled Trials of the Cochrane Library, and the American Society of Clinical Oncology database were searched for relevant studies. The primary outcomes were any grade adverse events (AEs) and grade ...[more]

PMID: 30787594

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Project description:Vancomycin and teicoplanin are the glycopeptides currently in use for the treatment of infections caused by invasive beta-lactam-resistant gram-positive organisms. We conducted a systematic review and meta-analysis of randomized controlled trials that have compared vancomycin and teicoplanin administered systemically for the treatment of suspected or proven infections. A comprehensive search of trials without year, language, or publication status restrictions was performed. The primary outcome was all-cause mortality. Two reviewers independently extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled by using the fixed-effect model (RRs of >1 favor vancomycin). Twenty-four trials were included. All-cause mortality was similar overall (RR, 0.95; 95% CI, 0.74 to 1.21), and there was no significant heterogeneity. In trials that used adequate allocation concealment, the results favored teicoplanin (RR, 0.82; 95% CI, 0.63 to 1.06), while in trials with unknown methods or inadequate concealment, the results favored vancomycin (RR, 3.61; 95% CI, 1.27 to 10.30). The latter trials might have recruited more severely ill patients. No other variable affected the RRs for mortality, including the assessment of glycopeptides administered empirically or for proven infections, neutropenia, the participant's age, and drug dosing. There were no significant differences between teicoplanin and vancomycin with regard to clinical failure (RR, 0.92; 95% CI, 0.81 to 1.05), microbiological failure (RR, 1.24; 95% CI, 0.93 to 1.65), and other efficacy outcomes. Lower RRs (in favor of teicoplanin) for clinical failure were observed with a lower risk of bias and when treatment was initiated for infections caused by gram-positive organisms rather than empirically. Total adverse events (RR, 0.61; 95% CI, 0.50 to 0.74), nephrotoxicity (RR, 0.44; 95% CI, 0.32 to 0.61), and red man syndrome were significantly less frequent with teicoplanin. Teicoplanin is not inferior to vancomycin with regard to efficacy and is associated with a lower adverse event rate than vancomycin.

Project description:BackgroundAs a successful treatment for hematological malignancy, chimeric antigen receptor T cells (CAR-T cells) have been expanded to solid tumors to demonstrate their safety and efficacy, especially for digestive system cancer (DSC). Various CAR-T cell constructs used in different types of DSCs result in heterogeneous responses. Thus, we aimed to systematically summarize the clinical response of DSCs treated with CAR-T cells and investigate factors associated with heterogeneity in outcomes.MethodsClinical studies of DSC patients treated with CAR-T cell therapy were selected from the PubMed, Cochrane, Embase, Web of Science databases before October 1, 2020. "CAR-T cell", "solid tumor" and their synonymous terms were used to construct the search strategy. Duplicates, reviews, non-English literature, articles not related to clinical studies or CAR-T cells used for digestive tumors were excluded. The included studies were assessed by the Institute of Health Economics (IHE) risk of bias tool to check the methodological quality. The inverse variance method was used to perform data pooling and subgroup analysis to clarify the causes of heterogeneity. Publication bias was examined by funnel plots and Egger's test.ResultsTwelve studies were included, and the risk of bias evaluation was demonstrated as plots using Review Manager 5.3. The pooled overall response rate (ORR) was 2% (95% CI: 0-6%), and the clinical benefit rate (CBR) was 42% (95% CI: 24-61%). According to subgroup analysis, costimulation (P=0.0449), lymphodepletion (P=0.0002), persistence of CAR-T cells (P=0.0443) and transduction method (P=0.0165) were factors contributing to heterogeneity. For adverse effects, pyrexia was the most frequent (35%, 95% CI: 24-61%). No publication bias was found, and the major results were robust within a slight fluctuation for each removal of one of the 12 studies.DiscussionCAR-T cell therapy is generally beneficial for patients with DSCs though the ORR was still poor. Modified construction with more specific tumor antigens, costimulatory domain and lentiviral vectors is necessary to obtain a better antitumor response of CAR-T cell therapy. Information of survival data are needed for a more comprehensive analysis.

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Safety and efficacy of atezolizumab in the treatment of cancers: a systematic review and pooled-analysis.

Publications

Safety and efficacy of atezolizumab in the treatment of cancers: a systematic review and pooled-analysis.

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