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

BackgroundWhile 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 sa...
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Autor*in:	Aya El Helali [verfasserIn] Jun Tao [verfasserIn] Charlene H. L. Wong [verfasserIn] Wendy Wing-Lok Chan [verfasserIn] Ka-Chun Mok [verfasserIn] Wing Fong Wu [verfasserIn] Kohei Shitara [verfasserIn] Markus Mohler [verfasserIn] Narikazu Boku [verfasserIn] Herbert Pang [verfasserIn] Ka On Lam [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI)

Übergeordnetes Werk:	In: Frontiers in Oncology - Frontiers Media S.A., 2012, 12(2022)
Übergeordnetes Werk:	volume:12 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fonc.2022.908026

Katalog-ID:	DOAJ08392440X

Internformat


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520			\|a BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829).
650		4	\|a advanced gastric adenocarcinoma
650		4	\|a immune checkpoint inhibition (ICI)
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650		4	\|a microsatellite instability (MSI)
653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
700	0		\|a Jun Tao \|e verfasserin \|4 aut
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700	0		\|a Herbert Pang \|e verfasserin \|4 aut
700	0		\|a Herbert Pang \|e verfasserin \|4 aut
700	0		\|a Ka On Lam \|e verfasserin \|4 aut
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allfields	10.3389/fonc.2022.908026 doi (DE-627)DOAJ08392440X (DE-599)DOAJc1baf14ea5aa46459a32b39d638e033e DE-627 ger DE-627 rakwb eng RC254-282 Aya El Helali verfasserin aut A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829). advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jun Tao verfasserin aut Charlene H. L. Wong verfasserin aut Wendy Wing-Lok Chan verfasserin aut Ka-Chun Mok verfasserin aut Wing Fong Wu verfasserin aut Kohei Shitara verfasserin aut Markus Mohler verfasserin aut Narikazu Boku verfasserin aut Herbert Pang verfasserin aut Herbert Pang verfasserin aut Ka On Lam verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 12(2022) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:12 year:2022 https://doi.org/10.3389/fonc.2022.908026 kostenfrei https://doaj.org/article/c1baf14ea5aa46459a32b39d638e033e kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2022.908026/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022
spelling	10.3389/fonc.2022.908026 doi (DE-627)DOAJ08392440X (DE-599)DOAJc1baf14ea5aa46459a32b39d638e033e DE-627 ger DE-627 rakwb eng RC254-282 Aya El Helali verfasserin aut A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829). advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jun Tao verfasserin aut Charlene H. L. Wong verfasserin aut Wendy Wing-Lok Chan verfasserin aut Ka-Chun Mok verfasserin aut Wing Fong Wu verfasserin aut Kohei Shitara verfasserin aut Markus Mohler verfasserin aut Narikazu Boku verfasserin aut Herbert Pang verfasserin aut Herbert Pang verfasserin aut Ka On Lam verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 12(2022) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:12 year:2022 https://doi.org/10.3389/fonc.2022.908026 kostenfrei https://doaj.org/article/c1baf14ea5aa46459a32b39d638e033e kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2022.908026/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022
allfields_unstemmed	10.3389/fonc.2022.908026 doi (DE-627)DOAJ08392440X (DE-599)DOAJc1baf14ea5aa46459a32b39d638e033e DE-627 ger DE-627 rakwb eng RC254-282 Aya El Helali verfasserin aut A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829). advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jun Tao verfasserin aut Charlene H. L. Wong verfasserin aut Wendy Wing-Lok Chan verfasserin aut Ka-Chun Mok verfasserin aut Wing Fong Wu verfasserin aut Kohei Shitara verfasserin aut Markus Mohler verfasserin aut Narikazu Boku verfasserin aut Herbert Pang verfasserin aut Herbert Pang verfasserin aut Ka On Lam verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 12(2022) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:12 year:2022 https://doi.org/10.3389/fonc.2022.908026 kostenfrei https://doaj.org/article/c1baf14ea5aa46459a32b39d638e033e kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2022.908026/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022
allfieldsGer	10.3389/fonc.2022.908026 doi (DE-627)DOAJ08392440X (DE-599)DOAJc1baf14ea5aa46459a32b39d638e033e DE-627 ger DE-627 rakwb eng RC254-282 Aya El Helali verfasserin aut A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829). advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jun Tao verfasserin aut Charlene H. L. Wong verfasserin aut Wendy Wing-Lok Chan verfasserin aut Ka-Chun Mok verfasserin aut Wing Fong Wu verfasserin aut Kohei Shitara verfasserin aut Markus Mohler verfasserin aut Narikazu Boku verfasserin aut Herbert Pang verfasserin aut Herbert Pang verfasserin aut Ka On Lam verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 12(2022) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:12 year:2022 https://doi.org/10.3389/fonc.2022.908026 kostenfrei https://doaj.org/article/c1baf14ea5aa46459a32b39d638e033e kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2022.908026/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022
allfieldsSound	10.3389/fonc.2022.908026 doi (DE-627)DOAJ08392440X (DE-599)DOAJc1baf14ea5aa46459a32b39d638e033e DE-627 ger DE-627 rakwb eng RC254-282 Aya El Helali verfasserin aut A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829). advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jun Tao verfasserin aut Charlene H. L. Wong verfasserin aut Wendy Wing-Lok Chan verfasserin aut Ka-Chun Mok verfasserin aut Wing Fong Wu verfasserin aut Kohei Shitara verfasserin aut Markus Mohler verfasserin aut Narikazu Boku verfasserin aut Herbert Pang verfasserin aut Herbert Pang verfasserin aut Ka On Lam verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 12(2022) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:12 year:2022 https://doi.org/10.3389/fonc.2022.908026 kostenfrei https://doaj.org/article/c1baf14ea5aa46459a32b39d638e033e kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2022.908026/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022
language	English
source	In Frontiers in Oncology 12(2022) volume:12 year:2022
sourceStr	In Frontiers in Oncology 12(2022) volume:12 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Frontiers in Oncology
authorswithroles_txt_mv	Aya El Helali @@aut@@ Jun Tao @@aut@@ Charlene H. L. Wong @@aut@@ Wendy Wing-Lok Chan @@aut@@ Ka-Chun Mok @@aut@@ Wing Fong Wu @@aut@@ Kohei Shitara @@aut@@ Markus Mohler @@aut@@ Narikazu Boku @@aut@@ Herbert Pang @@aut@@ Ka On Lam @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	684965518
id	DOAJ08392440X
language_de	englisch
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This meta-analysis aimed to quantify the efficacy and safety of ICI and explore potential predictive tumor tissue biomarkers in aGC.MethodsA 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.ResultsA 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 &lt;0.00001) and TMB-high (P &lt;0.0001) tumors derived favorable survival benefits from ICIs.Conclusions and relevanceThe results of this meta-analysis suggest that ICIs result in improved OS outcomes in aGC. 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callnumber-first	R - Medicine
author	Aya El Helali
spellingShingle	Aya El Helali misc RC254-282 misc advanced gastric adenocarcinoma misc immune checkpoint inhibition (ICI) misc PD-L1 misc tumor mutational burden (TMB) misc microsatellite instability (MSI) misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
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topic_title	RC254-282 A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer advanced gastric adenocarcinoma immune checkpoint inhibition (ICI) PD-L1 tumor mutational burden (TMB) microsatellite instability (MSI)
topic	misc RC254-282 misc advanced gastric adenocarcinoma misc immune checkpoint inhibition (ICI) misc PD-L1 misc tumor mutational burden (TMB) misc microsatellite instability (MSI) misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc advanced gastric adenocarcinoma misc immune checkpoint inhibition (ICI) misc PD-L1 misc tumor mutational burden (TMB) misc microsatellite instability (MSI) misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
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title_full	A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
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author_browse	Aya El Helali Jun Tao Charlene H. L. Wong Wendy Wing-Lok Chan Ka-Chun Mok Wing Fong Wu Kohei Shitara Markus Mohler Narikazu Boku Herbert Pang Ka On Lam
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title_sort	meta-analysis with systematic review: efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
callnumber	RC254-282
title_auth	A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
abstract	BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829).
abstractGer	BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829).
abstract_unstemmed	BackgroundWhile 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.MethodsA 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.ResultsA 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 relevanceThe 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 TMBSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42019137829).
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title_short	A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer
url	https://doi.org/10.3389/fonc.2022.908026 https://doaj.org/article/c1baf14ea5aa46459a32b39d638e033e https://www.frontiersin.org/articles/10.3389/fonc.2022.908026/full https://doaj.org/toc/2234-943X
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author2	Jun Tao Charlene H. L. Wong Wendy Wing-Lok Chan Ka-Chun Mok Wing Fong Wu Kohei Shitara Markus Mohler Narikazu Boku Herbert Pang Ka On Lam
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