A meta-analysis of the comparing of the first-generation and next-generation TKIs in the treatment of NSCLC

Yongxing Li; Jianye Yang; Yufen Xu; Ming Zhang; Xiaoping Zhang; Wenyu Chen; Xiaodong Lv; Yongxing Li; Jianye Yang; Yufen Xu; Ming Zhang; Xiaoping Zhang; Wenyu Chen; Xiaodong Lv

doi:10.3934/mbe.2019283

Mathematical Biosciences and Engineering

2019, Volume 16, Issue 5: 5687-5696. doi: 10.3934/mbe.2019283

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Research article Special Issues

A meta-analysis of the comparing of the first-generation and next-generation TKIs in the treatment of NSCLC

1.
Department of Respiration, Shaoxing Municipal Hospital, Affiliated Hospital of Shaoxing University, Shaoxing 312000, Zhejiang, China
2.
Department of Oncology, The First Hospital of Jiaxing, First Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, China
3.
Department of Respiration, The First Hospital of Jiaxing, First Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, China
4.
Division of Science and Education, The First Hospital of Jiaxing, First Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, China

Received: 13 March 2019 Accepted: 16 May 2019 Published: 18 June 2019

BackgroundThe current standard approach to the treatment of patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)—sensitizing mutations has been the treatment with a first-generation EGFR-TKIs. While, with resistance developed against first-generation EGFR-TKIs, second/third-generation TKIs have attracted all the attention, and replaced first-generation EGFR- TKIs upon disease progression due to the greater efficacy and more favorable tolerability. In the past few years, this strategy has been challenged by clinical evidence when next-generation EGFR-TKIs are used in patients with advanced NSCLC.

ObjectiveIn this study, we performed a meta- analysis to investigate the efficacy of next-generation TKIs comparison with first-generation TKIs in the treatment of NSCLC.

MethodsThe multiple databases including Pubmed, Embase, Cochrane library databases were adopted to search for the relevant studies, and full-text articles involving to comparison of next-generation TKIs and first-generation TKIs were reviewed. After rigorous reviewing on quality, the data was extracted from eligible randomized controlled trial (RCT). Meta-analysis Revman 5.3 software was used to analyze the combined pooled ORs with the corresponding 95% confidence interval using fixed- or random-effects models according to the heterogeneity.

ResultsA total of 5 randomized controlled trials were included in this analysis. The group of next-generation TKIs did achieved benefit in progression-free survival (PFS) (OR = 0.58, 95%CI = 0.45-0.75, P < 0.0001), overall survival (OS) (OR = 0.76, 95%CI = 0.65-0.90, P = 0.001) as well with the objective response rate (ORR) (OR = 1.27, 95%CI = 1.01-1.61, P = 0.04), respectively. In the results of subgroup analysis of PFS with EGFR mutations, there is also significant differences with exon 19 deletion (OR = 0.56, 95%CI = 0.41-0.77, P = 0.0003) and exon 21 (L858R) mutation (OR = 0.60, 95%CI = 0.49-0.75, P < ＝0.00001). While, the treatment-related severe adverse event (SAE) between the next-generation TKIs and first-generation TKIs did not have statistical significance (OR = 1.48, 95%CI = 0.62-3.55, P = 0.38).

ConclusionThe next-generation TKIs significantly improved efficacy outcomes in the treatment of EGFR mutation-positive advanced NSCLC compared with the first-generation TKIs, with a manageable safety profile. These results are potentially important for clinical decision making for these patients.
- NSCLC,
- first-generation EGFR-TKIs,
- second/third-generation EGFR-TKIs,
- meta-analysis
Citation: Yongxing Li, Jianye Yang, Yufen Xu, Ming Zhang, Xiaoping Zhang, Wenyu Chen, Xiaodong Lv. A meta-analysis of the comparing of the first-generation and next-generation TKIs in the treatment of NSCLC[J]. Mathematical Biosciences and Engineering, 2019, 16(5): 5687-5696. doi: 10.3934/mbe.2019283

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Abstract

BackgroundThe current standard approach to the treatment of patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)—sensitizing mutations has been the treatment with a first-generation EGFR-TKIs. While, with resistance developed against first-generation EGFR-TKIs, second/third-generation TKIs have attracted all the attention, and replaced first-generation EGFR- TKIs upon disease progression due to the greater efficacy and more favorable tolerability. In the past few years, this strategy has been challenged by clinical evidence when next-generation EGFR-TKIs are used in patients with advanced NSCLC.

ObjectiveIn this study, we performed a meta- analysis to investigate the efficacy of next-generation TKIs comparison with first-generation TKIs in the treatment of NSCLC.

MethodsThe multiple databases including Pubmed, Embase, Cochrane library databases were adopted to search for the relevant studies, and full-text articles involving to comparison of next-generation TKIs and first-generation TKIs were reviewed. After rigorous reviewing on quality, the data was extracted from eligible randomized controlled trial (RCT). Meta-analysis Revman 5.3 software was used to analyze the combined pooled ORs with the corresponding 95% confidence interval using fixed- or random-effects models according to the heterogeneity.

ResultsA total of 5 randomized controlled trials were included in this analysis. The group of next-generation TKIs did achieved benefit in progression-free survival (PFS) (OR = 0.58, 95%CI = 0.45-0.75, P < 0.0001), overall survival (OS) (OR = 0.76, 95%CI = 0.65-0.90, P = 0.001) as well with the objective response rate (ORR) (OR = 1.27, 95%CI = 1.01-1.61, P = 0.04), respectively. In the results of subgroup analysis of PFS with EGFR mutations, there is also significant differences with exon 19 deletion (OR = 0.56, 95%CI = 0.41-0.77, P = 0.0003) and exon 21 (L858R) mutation (OR = 0.60, 95%CI = 0.49-0.75, P < ＝0.00001). While, the treatment-related severe adverse event (SAE) between the next-generation TKIs and first-generation TKIs did not have statistical significance (OR = 1.48, 95%CI = 0.62-3.55, P = 0.38).

ConclusionThe next-generation TKIs significantly improved efficacy outcomes in the treatment of EGFR mutation-positive advanced NSCLC compared with the first-generation TKIs, with a manageable safety profile. These results are potentially important for clinical decision making for these patients.

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