Meta-analysis of genetic polymorphisms in programmed cell death 1

2014 ◽  
Vol 74 (3) ◽  
pp. 230-239 ◽  
Author(s):  
Y.H. Lee ◽  
S.-C. Bae ◽  
J.-H. Kim ◽  
G.G. Song
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Genetic Polymorphisms ◽  
Meta Analysis ◽  
Programmed Cell Death 1

Immunotherapy efficacy of programmed cell death 1 (PD-1) versus programmed death ligand-1 (PD-L1) inhibitors in non-small cell lung cancer (NSCLC) patients: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21700-e21700
Author(s):  
Danrong Yang ◽  
Longgang Cui ◽  
Yuzi Zhang ◽  
Zhengyi Zhao ◽  
Yuezong Bai
Keyword(s):  
Systematic Review ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Meta Analysis ◽  
Small Cell ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Line Therapy ◽  
Programmed Cell Death 1 ◽  
The Difference

e21700 Background: Immune checkpoint inhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have been new standard of care for non-small cell cancer patients. However, little is known about the difference in efficacy between these two types of drugs. In this study, we aimed to assess the differences between anti-PD-1 and anti-PD-L1 in NSCLC treatment through a systematic review and meta-analysis. Methods: We systematically searched PubMed, CENTRAL, and Embase from January, 2000 to November, 2019. We also reviewed abstracts and presentations from all major conference proceedings. All randomized controlled trials that compared anti-PD-1/anti-PD-L1 with standard treatment in NSCLC cancer patients were selected as candidates. Studies with anti-PD-1 and anti-PD-L1 were screened and paired upon the mirror principle. The primary outcome was the difference in overall survival (OS). As the main results, indirect comparison of anti-PD-1 and anti-PD-L1 were calculated for each mirror group and then pooled using a random-effects model. Results: 16 randomized controlled trials were included for the meta-analysis. Overall, anti-PD-1 exhibited superior OS (HR 0.80, 95% CI 0.68-0.95, P= .01) over anti-PD-L1. Subgroup analysis showed that anti-PD-1 exhibited superior OS over anti-PD-L1 ICIs in combination therapy (HR 0.67, 95% CI 0.54-0.82, P <.01), but not in monotherapy (HR 0.89, 95% CI 0.74-1.06), 2nd line therapy (HR 0.84, 95% CI 0.66-1.06) or 1st line therapy (HR 0.77, 95% CI 0.58-1.03). Conclusions: The results demonstrated that anti-PD-1 exhibited favorable survival outcomes compared to anti-PD-L1 in NSCLC treatment, which provides an important guide for clinicians.

Programmed Cell Death 1 (PD-1) Ligand (PD-L1) Expression in Solid Tumors As a Predictive Biomarker of Benefit From PD-1/PD-L1 Axis Inhibitors: A Systematic Review and Meta-Analysis

2017 ◽  
pp. 1-15 ◽  
Author(s):  
Monica Khunger ◽  
Adrian V. Hernandez ◽  
Vinay Pasupuleti ◽  
Sagar Rakshit ◽  
Nathan A. Pennell ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Immune Cell ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell Lung ◽  
Programmed Cell Death 1 ◽  
Tumor Types

Purpose Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway show significant clinical activity across several tumor types. However, a majority of patients do not respond to these agents. Use of biomarker assays to predict response to these agents is an active area of research; however, the predictive value of PD-L1 immunohistochemistry (IHC) assays is largely inconsistent across clinical trials. In this meta-analysis of clinical trials of PD-1/PD-L1–targeted agents, we evaluate the predictive value of a tumor and tumor-infiltrating immune cell PD-L1 IHC assay as a biomarker for objective response to PD-1/PD-L1 inhibitors. Methods We searched databases (PubMed, Medline, ASCO abstracts, European Society for Medical Oncology abstracts, and Scopus) up until December 2016 for clinical trials using PD-1/PD-L1 inhibitors with reported PD-L1 biomarker data. Objective response rates (primary end point) from all phase I to III trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab in advanced solid tumors were collected. Odds ratios (ORs) for response in PD-L1–positive patients compared with PD-L1–negative patients were calculated using the DerSimonian-Laird random effects model to combine trials. We performed meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Forty-one distinct trials with 6,664 patients were identified. PD-L1 expression was predictive of favorable response across all tumor types (OR, 2.26; 95% CI, 1.85 to 2.75; P < .001), with the significantly largest effect observed in non–small-cell lung cancer (OR, 2.51; 95% CI, 1.99 to 3.17; P < .001). A subgroup analysis across all non–small-cell lung cancer trials using nivolumab and Dako clone 28-8 (Dako, Carpinteria, CA) IHC antibody assay yielded a significantly higher objective response rate in patients with tumor PD-L1 expression even at the minimum cutoff value of 1% (OR, 2.17; 95% CI, 1.03 to 4.57). Conclusion Our meta-analysis shows that tumor and tumor-infiltrating immune cell PD-L1 overexpression based on IHC is associated with significantly higher response rates to PD-1/PD-L1 axis inhibitors across a range of malignant solid tumors.

scholarly journals Association between PD-1 and PD-L1 Polymorphisms and the Risk of Cancer: A Meta-Analysis of Case-Control Studies

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1150 ◽  
Author(s):  
Mohammad Hashemi ◽  
Shima Karami ◽  
Sahel Sarabandi ◽  
Abdolkarim Moazeni-Roodi ◽  
Andrzej Małecki ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Risk ◽  
Programmed Cell Death ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
Programmed Cell Death 1 ◽  
Risk Of Cancer ◽  
The Impact

A number of case-control studies regarding the association of the polymorphisms in the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) genes with the risk of cancer have yielded inconsistent findings. Therefore, we have conducted a comprehensive, updated meta-analysis study to identify the impact of PD-1 and PD-L1 polymorphisms on overall cancer susceptibility. The findings revealed that PD-1 rs2227981 and rs11568821 polymorphisms significantly decreased the overall cancer risk (Odds Ratio (OR) = 0.82, 95% CI = 0.68–0.99, p = 0.04, TT vs. CT+CC; OR = 0.79, 95% CI = 0.67–0.94, p = 0.006, AG vs. GG, and OR = 0.82, 95% CI = 0.70–0.96, p = 0.020, AG+AA vs. GG, respectively), while PD-1 rs7421861 polymorphism significantly increased the risk of developing cancer (OR = 1.16, 95% CI = 1.02–1.33, p = 0.03, CT vs. TT). The PD-L1 rs4143815 variant significantly decreased the risk of cancer in homozygous (OR = 0.62, 95% CI = 0.41–0.94, p = 0.02), dominant (OR = 0.70, 95% CI = 0.50–0.97, p = 0.03), recessive (OR = 0.76, 95% CI = 0.60–0.96, p = 0.02), and allele (OR = 0.78, 95% CI = 0.63–0.96, p = 0.02) genetic models. No significant association between rs2227982, rs36084323, rs10204525, and rs2890658 polymorphisms and overall cancer risk has been found. In conclusions, the results of this meta-analysis have revealed an association between PD-1 rs2227981, rs11568821, rs7421861, as well as PD-L1 rs4143815 polymorphisms and overall cancer susceptibility.

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