The relationship between pneumonitis and programmed cell death-1/programmed cell death ligand 1 inhibitors among cancer patients: A systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Xu D
PROVIDER: S-EPMC7544380 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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The relationship between pneumonitis and programmed cell death-1/programmed cell death ligand 1 inhibitors among cancer patients: A systematic review and meta-analysis.
Xu Dongmei D Liu Hongmei H Xiang Meiyi M Feng Alei A Tian Mei M Li Donghua D Mao Yantao Y Zhang Li L Zhang Shuisheng S Tian Yuan Y
Medicine 20201001 41
<h4>Background</h4>We put the meta-analysis into practice to reveal the relationship between the incidence risk of immune-related pneumonitis and the use of programmed cell death-1 (PD-1) and ligand 1 (PD-L1) inhibitors related pneumonitis in cancer patients.<h4>Method</h4>The meta-analysis was put into practice according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Odds ratio (OR) was evaluated by random effect model.<h4>Results</h4>After screening and e ...[more]
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Project description:ImportanceImmune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice.ObjectiveTo assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types.Data sourcesSystematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed.Study selectionAll randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups.Data extraction and synthesisThree investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis.Main outcomes and measuresDifferences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model.ResultsNineteen randomized clinical trials involving 11 379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P < .001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P = .02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies.Conclusions and relevanceComprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.
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Project description:BackgroundProgrammed cell death ligand 1 (PD-L1), which is highly expressed in a variety of malignant tumors, is closely related to clinicopathological features and prognosis. However, there are few studies on the potential effects of PD-L1 on thyroid carcinoma, the incidence of which has shown an upward trend worldwide. This study aimed to explore the association between PD-L1 expression and clinicopathological features and prognosis of thyroid cancer.MethodsAn elaborate retrieval was performed using Medline, PubMed, Cochrane Library, EMBASE, Web of Science, WanFang databases, and China National Knowledge Infrastructure to determine the association between PD-L1 expression and disease-free survival (DFS), overall survival (OS), and clinicopathological features in patients with thyroid cancer. Study selection, data extraction, risk assessment, and data synthesis were performed independently by 2 reviewers. In this meta-analysis, RevMan 5.3 and Stata 15.1 were used for bias risk assessment and data synthesis.ResultsAfter a detailed search, 2546 cases reported in 13 articles were included in this meta-analysis. The outcomes revealed that high expression of PD-L1 in patients with thyroid cancer was associated with poor DFS (hazard ratio [HR] = 3.37, 95% confidence interval [CI] 2.54-4.48, P < .00001) and OS (HR = 2.52, 95% CI: 1.20-5.32, P = .01). High PD-L1 expression was associated with tumor size ≥2 cm, tumor recurrence, extrathyroidal extension, concurrent thyroiditis, unifocal tumor, and absence of psammoma body (P < .05). Subgroup analysis showed that positive expression of PD-L1 was related to poor prognosis for DFS of non-medullary thyroid carcinoma, and the overexpression of PD-L1 in differentiated thyroid carcinoma (DTC) was related to tumor recurrence, concurrent thyroiditis, extrathyroidal extension, unifocal DTC, late stage DTC, and BRAFV600E mutation in DTC.ConclusionPD-L1 is a significant predictor of prognosis and malignancy of thyroid cancer (especially DTC), and PD-L1 inhibitors may be a promising therapeutic option for refractory thyroid cancer in the future.
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Project description:PurposeTo evaluate the incidence risk of programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitor-related alopecia for cancer patients, the meta-analysis was put into practice.MethodThe meta-analysis was designed and put into practice according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.ResultsAfter rigorous screening and verification, 22 clinical trials involving PD-1/PD-L1 inhibitors were collected for the final comprehensive analysis. The incidence risk of alopecia for all-grade in the PD-1/PD-L1 group was significantly lower than that in the control chemotherapy group (odds ratio [OR] = 0.01, 95% confidence interval [CI]: [0.01, 0.04], I = 86%, Z = 8.73 [P < .00001]). Similar to the above, the incidence risk of alopecia for grade 3-5 related to PD-1/PD-L1 was obvious lower than the control group (OR = 0.17, 95% CI:[0.05, 0.55], I = 0%, Z = 2.97 [P = .003]). When 7 clinical trials (PD-1/PD-L1 + Chemotherapy vs Chemotherapy) were taken to evaluate the risk of alopecia for all-grade and grade 3-5, no statistically significant results were found.ConclusionThe incidence risk of alopecia caused by PD-1/PD-L1 is significantly lower than chemotherapy, and there is no statistical significant evidence that PD-1/PD-L1 combined with chemotherapy would increase the incidence risk of alopecia.
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Project description:Background An influx of systematic reviews (SRs) of programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) checkpoint inhibitors in cancer treatment with or without meta-analysis and with different methodological quality and inconsistent results have been published, confusing clinical decision making. The aim of this study was to comprehensively evaluate and summarize the current evidence of PD-(L)1 inhibitors in the treatment of cancer. Methods A comprehensive search of SRs, which included meta-analyses of PD-(L)1 inhibitors on cancer, was performed on eight databases with a cutoff date of 1 January 2022. Two authors independently identified SRs, extracted data, assessed the report quality according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, evaluated the methodological quality by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and appraised the quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results A total of 172 SRs with meta-analysis met the inclusion criteria. The report quality of included SRs was quite good, with 128 (74.42%) SRs of high quality and 44 (25.58%) of moderate quality. The methodological quality was alarming, as only one (0.58%) SR had high quality, five (2.91%) SRs had low quality, and the other 166 (96.51%) SRs had critically low quality. For GRADE, 38 (3.77%) outcomes had high-quality evidence, 288 (28.57%) moderate, 545 (54.07%) low, and 137 (13.59%) critically low-quality evidence. Current evidence indicated that treatment with PD-(L)1 inhibitors were significantly effective in non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, malignant melanoma, renal cell carcinoma, and urothelial carcinoma, breast cancer, and head and neck squamous cell carcinoma with PD-L1 expression level≥1%, whereas the evidence in gastroesophageal and colorectal tumors is still controversial. Monotherapy with PD-(L)1 inhibitors was associated with a lower frequency of any grade and high-grade adverse events (AEs). The incidence of any grade and high-grade AEs caused by PD-(L)1 inhibitors in combination with other therapies was no lower than the controls. However, PD-(L)1 inhibitors were associated with a higher frequency of any grade and high-grade immune-related AEs. Conclusions PD-(L)1 inhibitors appeared to be effective and safe for cancer treatment, except for gastrointestinal tumors; however, the quality of the evidence is not convincing. Future studies should improve methodological quality and focus on the sequential trial analysis of subgroups and safety. Systematic Review Registration http://www.crd.york.ac.uk/prospero, identifier CRD42020194260.
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