scholarly journals Predictive effect of molecular and clinical characteristics for the OS and PFS efficacy of anti-PD-1/PD-L1 immunotherapy in patients with NSCLC: a meta-analysis and systematic review

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e047663
Author(s):  
Rui An ◽  
Feng Zhao ◽  
Liqian Wang ◽  
Jikang Shan ◽  
Xianjun Wang
Keyword(s):  
Systematic Review ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Clinical Characteristics ◽  
Meta Analysis ◽  
Objective Response ◽  
Smoking History ◽  
Secondary Outcome ◽  
Secondary Outcome Measure ◽  
Predictive Effect

ObjectiveTo evaluate the predictive effect of molecular and clinical characteristics for the efficacy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand-1 (PD-L1) immunotherapy in patients with non-small cell lung cancer (NSCLC).DesignSystematic review and meta-analysis.SettingTwelve randomised controlled trials (RCTs) with 7442 patients were retrieved from all over the world.MethodsElectronic databases were searched for eligible RCTs. The HRs and 95% CIs for overall survival (OS) and progression‐free survival (PFS) for the whole and subgroup population were extracted for meta-analysis using Review Manager V.5.3 software.Primary and secondary outcome measureOS was the primary outcome and PFS was the secondary outcome.ResultsTwelve RCTs with 7442 patients were included. For the trial population, anti-PD-1/PD-L1 immunotherapy significantly improved OS (HR=0.78, 95% CI 0.70 to 0.86, p<0.00001) and objective response rate (ORR) (risk ratio=1.37, 95% CI 1.08 to 1.74, p=0.009). Subgroup analysis results showed an improved OS at PD-L1≥1%, ≥5% and ≥50% levels, and a longer PFS at PD-L1≥5% and ≥50% levels. Moreover, OS and PFS benefits were observed in the non-first line treatment, squamous cell carcinoma histology, male, smoking, non-central nervous system (CNS) metastasis, epidermal growth factor receptor (EGFR) wild-type and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant subgroups.ConclusionsAnti-PD-1/PD-L1 immunotherapy significantly improved OS and ORR and reduced the rate of Adverse Events (AEs) compared to chemotherapy. PD-L1 expression, line of therapy, histology, sex, smoking history, CNS metastases, EGFR and KRAS mutational status might be potential predictors for the therapeutic effect of anti-PD-1/PD-L1 immunotherapy in specific patients with NSCLC.

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 Anti–Programmed Cell Death (PD)-1 Immunotherapy for Malignant Tumor: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 9 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Ran Chen ◽  
Pei-Chun Peng ◽  
Bin Wen ◽  
Fu-Ying Li ◽  
Sheng Xie ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Malignant Tumor ◽  
Meta Analysis
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