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Comparison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment: a meta-analysis

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Abstract

Purpose

Exon 19 deletion and exon 21 L858R mutation were the most common epidermal growth factor receptor (EGFR) mutations. We examined the clinical impact of these two mutations in patients with non-small-cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) treatment.

Methods

The outcomes of interest were progression-free survival (PFS), overall survival (OS) and objective response rates (ORR), network meta-analysis and direct meta-analysis were conducted to calculate the efficacy of EGFR-TKIs between these two mutations. We also investigated the association between EGFR mutation types and clinical characteristics.

Results

A total of 4835 patients from 26 trials were assessed. EGFR-TKIs, compared with chemotherapy, significantly prolonged PFS and OS in both exon 19 deletion and exon 21 L858R mutation based on 8 trials. Network meta-analysis revealed that treatment with EGFR-TKIs had greater benefit in exon 19 deletion than in exon 21 L858R mutation. Furthermore, direct meta-analysis from 12 studies showed the similar result; patients with exon 19 deletion had a significantly longer PFS compared with exon 21 L858R mutation (HR, 0.69; 95 % CI, 0.57–0.82; P < 0.001). There were also greater benefit on OS (HR, 0.61; 95 % CI, 0.43–0.86; P = 0.005) and higher ORR (OR, 2.14; 95 % CI, 1.63–2.81; P < 0.001). Additionally, we found that a significant association between the type of mutation and age (P < 0.001) or smoking status (P = 0.022), but no other significant differences were detected in sex, histologic subtype and performance status between these two mutations.

Conclusions

Patients with NSCLC and EGFR exon 19 deletion had a longer PFS, OS and higher response rates after EGFR-TKI therapy compared with exon 21 L858R mutation.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (grant number 81560451), Kunming University of Science and Technology Talent Introduction Fund (grant number KKSY201560001) and National Laboratory Special Fund (grant number 2060204).

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Authors and Affiliations

  1. Laboratory of Molecular Genetics of Aging & Tumor, Medical Faculty, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming, Yunnan, 650500, China

    Miaomiao Sheng, Fang Wang, Yueguang Zhao, Shanshan Li, Ying Luo & Wenru Tang

  2. First People’s Hospital of Yunnan Province, 157 Jinbi Road, Kunming, Yunnan, 650032, China

    Xiaojie Wang & Tao Shou

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  1. Miaomiao Sheng
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Sheng, M., Wang, F., Zhao, Y. et al. Comparison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment: a meta-analysis. Eur J Clin Pharmacol 72, 1–11 (2016). https://doi.org/10.1007/s00228-015-1966-0

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