Research Papers:

Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2

Masayuki Takeda _, Kazuko Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Junko Tanizaki, Takayuki Takahama, Koji Haratani, Kazuto Nishio and Kazuhiko Nakagawa

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Oncotarget. 2018; 9:21132-21140. https://doi.org/10.18632/oncotarget.24958

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Masayuki Takeda1, Kazuko Sakai2, Hidetoshi Hayashi1, Kaoru Tanaka1, Junko Tanizaki1, Takayuki Takahama1, Koji Haratani1, Kazuto Nishio2 and Kazuhiko Nakagawa1

1Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

2Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

Correspondence to:

Masayuki Takeda, email: [email protected]

Keywords: epidermal growth factor receptor gene (EGFR); human epidermal growth factor receptor 2 gene (HER2); resistance; lung cancer; nivolumab

Received: November 03, 2017     Accepted: March 15, 2018     Published: April 20, 2018


Unlike common epidermal growth factor receptor gene (EGFR) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene (HER2) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel. Between July 2013 and June 2017, 206 patients with pathologically confirmed lung cancer were screened for genetic alterations including HER2 and EGFR mutations. Ten patients harbored HER2 exon-20 insertions (one of whom also carried an exon-19 deletion of EGFR), and 12 patients harbored EGFR exon-20 mutations. Five of the 13 patients with EGFR mutations were treated with EGFR-TKIs, two of whom manifested a partial response, two stable disease, and one progressive disease. Among the seven patients treated with nivolumab, one patient manifested a partial response, three stable disease, and three progressive disease, with most (86%) of these patients discontinuing treatment as a result of disease progression within 4 months. The H1047R mutation of PIK3CA detected in one patient was the only actionable mutation coexisting with the exon-20 mutations of EGFR or HER2. Potentially actionable mutations thus rarely coexist with exon-20 mutations of EGFR or HER2, and EGFR-TKIs and nivolumab show limited efficacy in patients with such exon-20 mutations.

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