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Article: A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer

TitleA meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
Authors
Keywordsadvanced gastric adenocarcinoma
immune checkpoint inhibition (ICI)
microsatellite instability (MSI)
PD-L1
tumor mutational burden (TMB)
Issue Date31-Oct-2022
PublisherFrontiers Media
Citation
Frontiers in Oncology, 2022, v. 12 How to Cite?
Abstract

Background: While the efficacy of immune checkpoint inhibitors (ICIs) is increasingly recognized in advanced gastric cancer (aGC), overall survival (OS) has not been consistently improved across the different randomized controlled trials (RCTs). This meta-analysis aimed to quantify the efficacy and safety of ICI and explore potential predictive tumor tissue biomarkers in aGC. Methods: A random-effect pairwise meta-analysis was used to evaluate the primary outcome of OS. Sensitivity analysis was performed to investigate the effects of ICIs on PD-L1 status, TMB, MSI-H, and the Asian patient population. We extracted the OS Kaplan-Meier curves from the included trials to compare the effect of PD-L1 status on response to ICIs using DigitizeIt 2.5 and Guyot's algorithm. Results: A pairwise meta-analysis of seven RCTs included in this study showed that ICIs were more effective than the comparator in improving OS (pooled HR: 0.84). We demonstrated that PD-1 ICIs were additive when combined with the comparator arm (pooled HR: 0.79). A sensitivity analysis showed that PD-1 ICIs were associated with better OS outcomes in the Asian patient population as monotherapy (pooled HR: 0.66) or in combination with chemotherapy (pooled HR: 0.83). We demonstrated that tumors with PD-L1 >= 1 (P = 0.02) and PD-L1 >= 10 (P = 0.006) derived OS benefit from ICI monotherapy. Equally, MSI-H (P < 0.00001) and TMB-high (P < 0.0001) tumors derived favorable survival benefits from ICIs. Conclusions and relevance: The results of this meta-analysis suggest that ICIs result in improved OS outcomes in aGC. The benefits varied with different ethnicities, class of ICI, PD-L1 expression, MSI status, and TMB


Persistent Identifierhttp://hdl.handle.net/10722/329128
ISSN
2023 Impact Factor: 3.5
2023 SCImago Journal Rankings: 1.066
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorEl Helali, A-
dc.contributor.authorTao, J-
dc.contributor.authorWong, CHL-
dc.contributor.authorChan, WWL-
dc.contributor.authorMok, KC-
dc.contributor.authorWu, WF-
dc.contributor.authorShitara, K-
dc.contributor.authorMohler, M-
dc.contributor.authorBoku, N-
dc.contributor.authorPang, HR-
dc.contributor.authorLam, KO-
dc.date.accessioned2023-08-05T07:55:30Z-
dc.date.available2023-08-05T07:55:30Z-
dc.date.issued2022-10-31-
dc.identifier.citationFrontiers in Oncology, 2022, v. 12-
dc.identifier.issn2234-943X-
dc.identifier.urihttp://hdl.handle.net/10722/329128-
dc.description.abstract<p> Background: While the efficacy of immune checkpoint inhibitors (ICIs) is increasingly recognized in advanced gastric cancer (aGC), overall survival (OS) has not been consistently improved across the different randomized controlled trials (RCTs). This meta-analysis aimed to quantify the efficacy and safety of ICI and explore potential predictive tumor tissue biomarkers in aGC. Methods: A random-effect pairwise meta-analysis was used to evaluate the primary outcome of OS. Sensitivity analysis was performed to investigate the effects of ICIs on PD-L1 status, TMB, MSI-H, and the Asian patient population. We extracted the OS Kaplan-Meier curves from the included trials to compare the effect of PD-L1 status on response to ICIs using DigitizeIt 2.5 and Guyot's algorithm. Results: A pairwise meta-analysis of seven RCTs included in this study showed that ICIs were more effective than the comparator in improving OS (pooled HR: 0.84). We demonstrated that PD-1 ICIs were additive when combined with the comparator arm (pooled HR: 0.79). A sensitivity analysis showed that PD-1 ICIs were associated with better OS outcomes in the Asian patient population as monotherapy (pooled HR: 0.66) or in combination with chemotherapy (pooled HR: 0.83). We demonstrated that tumors with PD-L1 >= 1 (P = 0.02) and PD-L1 >= 10 (P = 0.006) derived OS benefit from ICI monotherapy. Equally, MSI-H (P < 0.00001) and TMB-high (P < 0.0001) tumors derived favorable survival benefits from ICIs. Conclusions and relevance: The results of this meta-analysis suggest that ICIs result in improved OS outcomes in aGC. The benefits varied with different ethnicities, class of ICI, PD-L1 expression, MSI status, and TMB <br></p>-
dc.languageeng-
dc.publisherFrontiers Media-
dc.relation.ispartofFrontiers in Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectadvanced gastric adenocarcinoma-
dc.subjectimmune checkpoint inhibition (ICI)-
dc.subjectmicrosatellite instability (MSI)-
dc.subjectPD-L1-
dc.subjecttumor mutational burden (TMB)-
dc.titleA meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer-
dc.typeArticle-
dc.identifier.doi10.3389/fonc.2022.908026-
dc.identifier.scopuseid_2-s2.0-85141956047-
dc.identifier.volume12-
dc.identifier.eissn2234-943X-
dc.identifier.isiWOS:000885070200001-
dc.identifier.issnl2234-943X-

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