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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000048
Original Articles

Effectiveness of Gefitinib against Non–Small-Cell Lung Cancer with the Uncommon EGFR Mutations G719X and L861Q

Watanabe, Satoshi MD, PhD*; Minegishi, Yuji MD, PhD; Yoshizawa, Hirohisa MD, PhD*; Maemondo, Makoto MD, PhD; Inoue, Akira MD, PhD§; Sugawara, Shunichi MD, PhD; Isobe, Hiroshi MD, PhD; Harada, Masao MD, PhD#; Ishii, Yoshiki MD, PhD**; Gemma, Akihiko MD, PhD; Hagiwara, Koichi MD, PhD††; Kobayashi, Kunihiko MD, PhD‡‡

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Abstract

Introduction:

In non–small-cell lung cancer, an exon 19 deletion and an L858R point mutation in the epidermal growth factor receptor (EGFR) are predictors of a response to EGFR-tyrosine kinase inhibitors. However, it is uncertain whether other uncommon EGFR mutations are associated with sensitivity to EGFR-tyrosine kinase inhibitors.

Methods:

A post-hoc analysis to assess prognostic factors was performed with the use of patients with EGFR mutations (exon 19 deletion, L858R, G719X, and L861Q) who were treated with gefitinib in the NEJ002 study, which compared gefitinib with carboplatin-paclitaxel as the first-line therapy.

Results:

In the NEJ002 study, 225 patients with EGFR mutations received gefitinib at any treatment line. The Cox proportional hazards model indicated that performance status, response to chemotherapy, response to gefitinib, and mutation types were significant prognostic factors. Overall survival (OS) was significantly shorter among patients with uncommon EGFR mutations (G719X or L861Q) compared with OS of those with common EGFR mutations (12 versus 28.4 months; p = 0.002). In the gefitinib group (n = 114), patients with uncommon EGFR mutations had a significantly shorter OS (11.9 versus 29.3 months; p < 0.001). By contrast, OS was similar between patients with uncommon mutations and those with common mutations in the carboplatin-paclitaxel group (n = 111; 22.8 versus 28 months; p = 0.358).

Conclusions:

The post-hoc analyses clearly demonstrated shorter survival for gefitinib-treated patients with uncommon EGFR mutations compared with the survival of those with common mutations and suggest that the first-line chemotherapy may be relatively effective for non–small-cell lung cancer with uncommon EGFR mutations.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Copyright © 2013 by the International Association for the Study of Lung Cancer

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