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

Objective To 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).Design Systematic review and meta-analysis.Setting Tw...

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Main Authors: Feng Zhao, Rui An, Liqian Wang, Jikang Shan, Xianjun Wang
Format: Article
Language:English
Published: BMJ Publishing Group 2021-12-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/12/e047663.full
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author Feng Zhao
Rui An
Liqian Wang
Jikang Shan
Xianjun Wang
author_facet Feng Zhao
Rui An
Liqian Wang
Jikang Shan
Xianjun Wang
author_sort Feng Zhao
collection DOAJ
description Objective To 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).Design Systematic review and meta-analysis.Setting Twelve randomised controlled trials (RCTs) with 7442 patients were retrieved from all over the world.Methods Electronic 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 measure OS was the primary outcome and PFS was the secondary outcome.Results Twelve 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.Conclusions Anti-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.
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spelling doaj-art-226f939004704e7f91a0be4f30ce934c2024-12-10T03:15:12ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2020-047663Predictive 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 reviewFeng Zhao0Rui An1Liqian Wang2Jikang Shan3Xianjun Wang4Department of Laboratory Medicine, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Laboratory Medicine, Affiliated Hangzhou First People`s Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Laboratory Medicine, Affiliated Hangzhou First People`s Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Laboratory Medicine, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Laboratory Medicine, Affiliated Hangzhou First People`s Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaObjective To 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).Design Systematic review and meta-analysis.Setting Twelve randomised controlled trials (RCTs) with 7442 patients were retrieved from all over the world.Methods Electronic 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 measure OS was the primary outcome and PFS was the secondary outcome.Results Twelve 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.Conclusions Anti-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.https://bmjopen.bmj.com/content/11/12/e047663.full
spellingShingle Feng Zhao
Rui An
Liqian Wang
Jikang Shan
Xianjun Wang
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://bmjopen.bmj.com/content/11/12/e047663.full
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