Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

BackgroundData on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant in...

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Autores principales:	Tian Tian, Min Yu, Juan Li, Maoqiong Jiang, Daiyuan Ma, Shubin Tang, Zhiyu Lin, Lin Chen, Youling Gong, Jiang Zhu, Qiang Zhou, Meijuan Huang, You Lu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	non–small cell lung cancer immune checkpoint inhibitor tyrosine kinase inhibitor epidermal growth factor receptor resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/69a13cda47364735a4dda48c6d0895f8
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spelling	oai:doaj.org-article:69a13cda47364735a4dda48c6d0895f82021-11-30T11:14:08ZFront-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation2234-943X10.3389/fonc.2021.739090https://doaj.org/article/69a13cda47364735a4dda48c6d0895f82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.739090/fullhttps://doaj.org/toc/2234-943XBackgroundData on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors.Materials and MethodsRelevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors.ResultsA total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05).ConclusionsTaken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.Tian TianMin YuJuan LiMaoqiong JiangDaiyuan MaShubin TangZhiyu LinLin ChenYouling GongJiang ZhuQiang ZhouMeijuan HuangYou LuFrontiers Media S.A.articlenon–small cell lung cancerimmune checkpoint inhibitortyrosine kinase inhibitorepidermal growth factor receptorresistanceNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	non–small cell lung cancer immune checkpoint inhibitor tyrosine kinase inhibitor epidermal growth factor receptor resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	non–small cell lung cancer immune checkpoint inhibitor tyrosine kinase inhibitor epidermal growth factor receptor resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tian Tian Min Yu Juan Li Maoqiong Jiang Daiyuan Ma Shubin Tang Zhiyu Lin Lin Chen Youling Gong Jiang Zhu Qiang Zhou Meijuan Huang You Lu Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation
description	BackgroundData on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors.Materials and MethodsRelevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors.ResultsA total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05).ConclusionsTaken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.
format	article
author	Tian Tian Min Yu Juan Li Maoqiong Jiang Daiyuan Ma Shubin Tang Zhiyu Lin Lin Chen Youling Gong Jiang Zhu Qiang Zhou Meijuan Huang You Lu
author_facet	Tian Tian Min Yu Juan Li Maoqiong Jiang Daiyuan Ma Shubin Tang Zhiyu Lin Lin Chen Youling Gong Jiang Zhu Qiang Zhou Meijuan Huang You Lu
author_sort	Tian Tian
title	Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation
title_short	Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation
title_full	Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation
title_fullStr	Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation
title_full_unstemmed	Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation
title_sort	front-line ici-based combination therapy post-tki resistance may improve survival in nsclc patients with egfr mutation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/69a13cda47364735a4dda48c6d0895f8
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Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

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