title: Clinical usefulness of gefitinib for non-small-cell lung cancer with a double epidermal growth factor receptor mutation.
abstract: The aim of this study was to investigate whether the pattern of epidermal growth factor receptor (EGFR) gene mutations affects sensitivity to gefitinib treatment. We investigated 44 surgically resected non-small-cell lung cancer (NSCLC) specimens obtained between 2001 and 2012 at the Tokyo Medical University Hospital. The specimens were obtained from patients treated with gefitinib as 1st-, 2nd-, or 3rd-line therapy for postoperative recurrent NSCLC. We detected EGFR mutations using the cycleave PCR technique. In addition, the specimens from non-responders were stained with antibodies against hepatocyte growth factor receptor (HGFR; MET) and hepatocyte growth factor (HGF). We assessed the progression of non-responders over a period of 2 months. Intermediate responders were considered to be patients who responded (exhibiting at least stable disease) to gefitinib therapy for 3-11 months, while long-term responders were defined as those who responded to gefitinib therapy for >12 months. The NSCLCs were histologically classified as 43 adenocarcinomas and one large-cell neuroendocrine carcinoma. One patient had an exon 18 point mutation, 23 an exon 19 deletion, 2 an exon 20 point mutation, 16 an exon 21 point mutation and 2 patients had both exon 20 and 21 point mutations. There were 4 non-responders, including the 2 patients with exon 20 mutation, 25 intermediate responders (including 10 patients under ongoing treatment) and 15 long-term responders (2 of whom are under ongoing treatment), including the 2 patients with both exon 20 and 21 mutations. Of the specimens obtained from non-responders, 3 stained with the anti- MET antibody and 1 stained with the anti-HGF antibody. Therefore, NSCLC with exon 20 mutation may respond to gefitinib treatment in the presence of an additional EGFR mutation.
authors: Chemotherapy Research Institute, Kaken Hospital, Ichikawa, Chiba 272-0827.
authors: Takefumi
authors: T
authors: Oikawa
authors: Department of Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors: Tatsuo
authors: T
authors: Ohira
authors: Department of Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors: Keishi
authors: K
authors: Otani
authors: Department of Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors: Masaru
authors: M
authors: Hagiwara
authors: Chemotherapy Research Institute, Kaken Hospital, Ichikawa, Chiba 272-0827.
authors: Chimori
authors: C
authors: Konaka
authors: Department of Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors: Norihiko
authors: N
authors: Ikeda
keywords: T790M; double mutation; gefitinib; non-small-cell lung cancer