A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer

Background: To date, no direct comparisons have been performed to compare the effectiveness of all epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) against EGFR mutation-positive non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of EGF...

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Main Authors: Jianqiong Yin, Jing Huang, Min Ren, Rui Tang, Linshen Xie, Jianxin Xue
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Cancer Pathogenesis and Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949713224000454
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author Jianqiong Yin
Jing Huang
Min Ren
Rui Tang
Linshen Xie
Jianxin Xue
author_facet Jianqiong Yin
Jing Huang
Min Ren
Rui Tang
Linshen Xie
Jianxin Xue
author_sort Jianqiong Yin
collection DOAJ
description Background: To date, no direct comparisons have been performed to compare the effectiveness of all epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) against EGFR mutation-positive non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of EGFR-TKIs in patients with EGFR mutation-positive NSCLC. Methods: We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Pooled estimations of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity (grade ≥ 3 adverse events) were performed within the Bayesian framework. Results: Twenty-three trials involving 11 treatments were included. All EGFR-TKIs improved PFS relative to chemotherapy, except for icotinib (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.26–1.44). All EGFR-TKIs demonstrated significant ORR benefits over chemotherapy. Osimertinib seemed to prolong PFS compared with icotinib (HR = 0.29, 95% CI: 0.1–0.86), gefitinib (HR = 0.39, 95% CI: 0.21–0.74), and erlotinib (HR = 0.53, 95% CI: 0.29–1.0). In addition, osimertinib showed favorable superiority in improving OS compared with chemotherapy (HR = 0.6, 95% CI: 0.43–0.82), gefitinib (HR = 0.61, 95% CI: 0.45–0.83), erlotinib (HR = 0.65, 95% CI: 0.48–0.89), and afatinib (HR = 0.65, 95% CI: 0.44–0.94). Among these regimens, afatinib showed the highest ORR (cumulative probability: 96.96%). Icotinib was associated with minimal toxicity among the EGFR-TKIs, followed by furmonertinib and osimertinib. Moreover, the toxicity spectra differed among the EGFR-TKIs. Subgroup analyses of patients with two common types of EGFR mutations indicated that furmonertinib possessed the greatest PFS benefit in patients with exon 19 deletion, and lazertinib showed the greatest PFS benefit in patients with Leu858Arg mutation. We also identified differences between EGFR-TKIs in prolonging PFS in patients with brain metastasis. Conclusions: Osimertinib is the first choice of treatment with considerable efficacy and safety for EGFR mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively.
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spelling doaj-art-b0bf3c3628854f39a6ca4aa1aa3d345a2025-08-20T02:53:13ZengElsevierCancer Pathogenesis and Therapy2949-71322025-03-013213514610.1016/j.cpt.2024.06.004A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancerJianqiong Yin0Jing Huang1Min Ren2Rui Tang3Linshen Xie4Jianxin Xue5Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaDepartment of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, ChinaAbdominal Oncology Ward, Division of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaDepartment of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaDepartment of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, The National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Corresponding author: Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.Background: To date, no direct comparisons have been performed to compare the effectiveness of all epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) against EGFR mutation-positive non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of EGFR-TKIs in patients with EGFR mutation-positive NSCLC. Methods: We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Pooled estimations of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity (grade ≥ 3 adverse events) were performed within the Bayesian framework. Results: Twenty-three trials involving 11 treatments were included. All EGFR-TKIs improved PFS relative to chemotherapy, except for icotinib (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.26–1.44). All EGFR-TKIs demonstrated significant ORR benefits over chemotherapy. Osimertinib seemed to prolong PFS compared with icotinib (HR = 0.29, 95% CI: 0.1–0.86), gefitinib (HR = 0.39, 95% CI: 0.21–0.74), and erlotinib (HR = 0.53, 95% CI: 0.29–1.0). In addition, osimertinib showed favorable superiority in improving OS compared with chemotherapy (HR = 0.6, 95% CI: 0.43–0.82), gefitinib (HR = 0.61, 95% CI: 0.45–0.83), erlotinib (HR = 0.65, 95% CI: 0.48–0.89), and afatinib (HR = 0.65, 95% CI: 0.44–0.94). Among these regimens, afatinib showed the highest ORR (cumulative probability: 96.96%). Icotinib was associated with minimal toxicity among the EGFR-TKIs, followed by furmonertinib and osimertinib. Moreover, the toxicity spectra differed among the EGFR-TKIs. Subgroup analyses of patients with two common types of EGFR mutations indicated that furmonertinib possessed the greatest PFS benefit in patients with exon 19 deletion, and lazertinib showed the greatest PFS benefit in patients with Leu858Arg mutation. We also identified differences between EGFR-TKIs in prolonging PFS in patients with brain metastasis. Conclusions: Osimertinib is the first choice of treatment with considerable efficacy and safety for EGFR mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively.http://www.sciencedirect.com/science/article/pii/S2949713224000454Non-small cell lung cancerEGFR-TKINetwork meta-analysisSurvivalToxicity
spellingShingle Jianqiong Yin
Jing Huang
Min Ren
Rui Tang
Linshen Xie
Jianxin Xue
A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer
Cancer Pathogenesis and Therapy
Non-small cell lung cancer
EGFR-TKI
Network meta-analysis
Survival
Toxicity
title A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer
title_full A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer
title_fullStr A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer
title_full_unstemmed A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer
title_short A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer
title_sort bayesian network meta analysis of egfr tyrosine kinase inhibitor treatments in patients with egfr mutation positive non small cell lung cancer
topic Non-small cell lung cancer
EGFR-TKI
Network meta-analysis
Survival
Toxicity
url http://www.sciencedirect.com/science/article/pii/S2949713224000454
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