The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis

Abstract Background The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the eff...

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Autores principales:	He Ba, Lei Liu, Qiang Peng, Jie Chen, Yao-dong Zhu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	PD-1 PD-L1 NSCLC Tumor mutation burden Blood Lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1cf3a60e35a64ae89845b53e7c9f72fa
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spelling	oai:doaj.org-article:1cf3a60e35a64ae89845b53e7c9f72fa2021-11-14T12:30:19ZThe relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis10.1186/s12885-021-08924-z1471-2407https://doaj.org/article/1cf3a60e35a64ae89845b53e7c9f72fa2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08924-zhttps://doaj.org/toc/1471-2407Abstract Background The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low. Methods PubMed, Embase, Cochrane, the Web of Science, and ClinicalTrials.gov were searched systematically from inception to February 2021 for studies of PD-1/PD-L1 inhibitors (durvalumab OR atezolizumab OR avelumab OR pembrolizumab OR Nivolumab) that provided hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS), or odds ratios (ORs) for objective response rate (ORR) in both bTMB high and bTMB low groups. Results A total of 2338 patients with advanced or metastatic NSCLC from six randomized controlled trials, which all used chemotherapy (CT) as a control, were included in this study. Compared with CT, PD-1/PD-L1 inhibitor therapy improved OS (HR 0.62, 95% CI 0.52–0.75, P < 0.01), PFS (HR 0.57, 95% CI 0.48–0.67, P < 0.01), and ORR (OR 2.69, 95% CI 1.84–3.93, P < 0.01) in bTMB-high NSCLC patients but not in bTMB-low patients (OS HR 0.86, 95% CI 0.69–1.07, P = 0.17; PFS HR 1.00, 95% CI 0.78–1.27, P = 0.98; ORR OR 0.63, 95% CI 0.49–0.80, P = 0.03). Subgroup analyses showed that these results were consistent across all subgroups (line of therapy, therapy regimen, type of NGS panel, PD-L1 expression, and cutoff value). Meta-regression analysis showed that the proportion of patients with squamous cell histology had no statistical effect on clinical outcomes. Sensitivity analyses illustrated that all results were stable. Conclusions The efficacy of PD-1/PD-L1 inhibitor therapy in advanced NSCLC patients may be dependent on bTMB level. Patients with high bTMB tend to obtain significantly better OS, PFS, and ORR from PD-1/PD-L1 inhibitor therapy than from CT. However, because of multiple limitations, including those related to reproducibility, the results are exploratory and should be interpreted with caution.He BaLei LiuQiang PengJie ChenYao-dong ZhuBMCarticlePD-1PD-L1NSCLCTumor mutation burdenBloodLung cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PD-1 PD-L1 NSCLC Tumor mutation burden Blood Lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	PD-1 PD-L1 NSCLC Tumor mutation burden Blood Lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 He Ba Lei Liu Qiang Peng Jie Chen Yao-dong Zhu The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
description	Abstract Background The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low. Methods PubMed, Embase, Cochrane, the Web of Science, and ClinicalTrials.gov were searched systematically from inception to February 2021 for studies of PD-1/PD-L1 inhibitors (durvalumab OR atezolizumab OR avelumab OR pembrolizumab OR Nivolumab) that provided hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS), or odds ratios (ORs) for objective response rate (ORR) in both bTMB high and bTMB low groups. Results A total of 2338 patients with advanced or metastatic NSCLC from six randomized controlled trials, which all used chemotherapy (CT) as a control, were included in this study. Compared with CT, PD-1/PD-L1 inhibitor therapy improved OS (HR 0.62, 95% CI 0.52–0.75, P < 0.01), PFS (HR 0.57, 95% CI 0.48–0.67, P < 0.01), and ORR (OR 2.69, 95% CI 1.84–3.93, P < 0.01) in bTMB-high NSCLC patients but not in bTMB-low patients (OS HR 0.86, 95% CI 0.69–1.07, P = 0.17; PFS HR 1.00, 95% CI 0.78–1.27, P = 0.98; ORR OR 0.63, 95% CI 0.49–0.80, P = 0.03). Subgroup analyses showed that these results were consistent across all subgroups (line of therapy, therapy regimen, type of NGS panel, PD-L1 expression, and cutoff value). Meta-regression analysis showed that the proportion of patients with squamous cell histology had no statistical effect on clinical outcomes. Sensitivity analyses illustrated that all results were stable. Conclusions The efficacy of PD-1/PD-L1 inhibitor therapy in advanced NSCLC patients may be dependent on bTMB level. Patients with high bTMB tend to obtain significantly better OS, PFS, and ORR from PD-1/PD-L1 inhibitor therapy than from CT. However, because of multiple limitations, including those related to reproducibility, the results are exploratory and should be interpreted with caution.
format	article
author	He Ba Lei Liu Qiang Peng Jie Chen Yao-dong Zhu
author_facet	He Ba Lei Liu Qiang Peng Jie Chen Yao-dong Zhu
author_sort	He Ba
title	The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
title_short	The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
title_full	The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
title_fullStr	The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
title_full_unstemmed	The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
title_sort	relationship between blood-based tumor mutation burden level and efficacy of pd-1/pd-l1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1cf3a60e35a64ae89845b53e7c9f72fa
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The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis

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