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Cancer Chemotherapy and Pharmacology

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01-12-2017 | Original Article

Uncommon mutation types of epidermal growth factor receptor and response to EGFR tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients

Authors: Kaiyan Chen, Xiaoqing Yu, Haiyang Wang, Zhiyu Huang, Yanjun Xu, Lei Gong, Yun Fan

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2017

Abstract

Purpose

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 L858R mutation) remains undetermined.

Methods

Seven hundred and fifty-five non-small cell lung cancer (NSCLC) patients with EGFR mutation analyses for TKI therapy were identified between October 2010 and December 2015 in East of China. And 66 patients bearing uncommon EGFR mutations were included to collect data from TKI response and prognosis. We categorised EGFR uncommon mutations as: sensitizing rare mutations (group 1: G719X, L861Q, S768I); Ex20 ins (group 2), or complex mutations (G719X + L861Q, G719X + S768I, 19 del + T790M, 19 del + L858R, L858R + S768I, and L858R + T790M; group 3).

Results

Of 66 patients given EGFR-TKI treatment, rare sensitive mutations, Ex20 ins, and complex mutations were identified in 37 (56.1%), 9 (13.6%), and 20 (33.3%) cases, respectively. TKI efficacy in patients harboring uncommon EGFR mutations exhibited a tumor response rate of 28.8% and a median progression-free survival (PFS) of 4.8 months. Additionally, patients with complex EGFR mutations had significantly longer PFS when compared with the remaining sensitizing rare mutations or Ex20 ins cases (8.6 vs. 4.1 vs. 3.1 months; p = 0.041). Importantly, complex EGFR mutations were independent predictors of increased overall survival (Hazard Ratios = 0.31; 95% confidence intervals: 0.11–0.90; p = 0.031). Among them, patients harboring Del-19 combined with L858R mutations showed a tendency to have higher response rate (RR) and improved PFS than those with other complex mutation patterns (RR: 66.7 vs. 14.3%, p = 0.021; PFS: 10.1 vs. 8.6 months, p = 0.232).

Conclusions

Personalized treatment should be evolving in different types of uncommon EGFR mutations. Clinical benefit from EGFR-TKIs was higher in NSCLC patients with complex EGFR mutations than those with other uncommon EGFR mutation types.

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Title: Uncommon mutation types of epidermal growth factor receptor and response to EGFR tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients
Authors: Kaiyan Chen
Xiaoqing Yu
Haiyang Wang
Zhiyu Huang
Yanjun Xu
Lei Gong
Yun Fan
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-017-3464-9

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