Clinical usefulness of gefitinib for non-small-cell lung cancer with a double epidermal growth factor receptor mutation
- Authors:
- Takefumi Oikawa
- Tatsuo Ohira
- Keishi Otani
- Masaru Hagiwara
- Chimori Konaka
- Norihiko Ikeda
View Affiliations
Affiliations: Chemotherapy Research Institute, Kaken Hospital, Ichikawa, Chiba 272‑0827, Japan, Department of Surgery, Tokyo Medical University, Tokyo 160-0023, Japan
- Published online on: November 10, 2014 https://doi.org/10.3892/mco.2014.455
-
Pages:
329-333
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
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.
View References
|
1
|
Lynch TJ, Bell DW, Sordella R, et al:
Activating mutations in the epidermal growth factor receptor
underlying responsiveness of non-small-cell lung cancer to
gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI
|
|
2
|
Paez JG, Janne PA, Lee JC, et al: EGFR
mutations in lung cancer: correlation with clinical response to
gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI
|
|
3
|
Inoue A, Suzuki T, Fukuhara T, et al:
Prospective phase II study of gefitinib for chemotherapy-naive
patients with advanced non-small-cell lung cancer with epidermal
growth factor receptor gene mutations. J Clin Oncol. 24:3340–3346.
2006. View Article : Google Scholar : PubMed/NCBI
|
|
4
|
Pao W, Miller VA, Politi KA, et al:
Acquired resistance of lung adenocarcinomas to gefitinib or
erlotinib is associated with a second mutation in the EGFR kinase
domain. PLoS Med. 2:e732005. View Article : Google Scholar : PubMed/NCBI
|
|
5
|
Kobayashi S, Boggon TJ, Dayaram T, et al:
EGFR mutation and resistance of non-small-cell lung cancer to
gefitinib. N Engl J Med. 352:786–792. 2005. View Article : Google Scholar : PubMed/NCBI
|
|
6
|
Engelman JA, Zejnullahu K, Mitsudomi T, et
al: MET amplification leads to gefitinib resistance in lung cancer
by activating ERBB3 signaling. Science. 316:1039–1043. 2007.
View Article : Google Scholar : PubMed/NCBI
|
|
7
|
Yano S, Wang W, Li Q, et al: Hepatocyte
growth factor induces gefitinib resistance of lung adenocarcinoma
with epidermal growth factor receptor-activating mutations. Cancer
Res. 68:9479–9487. 2008. View Article : Google Scholar : PubMed/NCBI
|
|
8
|
Nguyen KS, Kobayashi S and Costa DB:
Acquired resistance to epidermal growth factor receptor tyrosine
kinase inhibitors in non-small-cell lung cancers dependent on the
epidermal growth factor receptor pathway. Clin Lung Cancer.
10:281–289. 2009. View Article : Google Scholar : PubMed/NCBI
|
|
9
|
Inukai M, Toyooka S, Ito S, et al:
Presence of epidermal growth factor receptor gene T790M mutation as
a minor clone in non-small cell lung cancer. Cancer Res.
66:7854–7858. 2006. View Article : Google Scholar : PubMed/NCBI
|
|
10
|
Tokumo M, Toyooka S, Ichihara S, et al:
Double mutation and gene copy number of EGFR in gefitinib
refractory non-small-cell lung cancer. Lung cancer. 53:117–121.
2006. View Article : Google Scholar : PubMed/NCBI
|
|
11
|
Wu JY, Wu SG, Yang CH, et al: Lung cancer
with epidermal growth factor receptor exon 20 mutations is
associated with poor gefitinib treatment response. Clin Cancer Res.
14:4877–4882. 2008. View Article : Google Scholar : PubMed/NCBI
|
|
12
|
Su KY, Chen HY, Li KC, et al: Pretreatment
epidermal growth factor receptor (EGFR) T790M mutation predicts
shorter EGFR tyrosine kinase inhibitor response duration in
patients with non-small-cell lung cancer. J Clin Oncol. 30:433–440.
2012. View Article : Google Scholar : PubMed/NCBI
|
|
13
|
Oxnard GR, Arcila ME, Chmielecki J,
Ladanyi M, Miller VA and Pao W: New strategies in overcoming
acquired resistance to epidermal growth factor receptor tyrosine
kinase inhibitors in lung cancer. Clin Cancer Res. 17:5530–5537.
2011. View Article : Google Scholar : PubMed/NCBI
|
|
14
|
Pao W and Ladanyi M: Epidermal growth
factor receptor mutation testing in lung cancer: searching for the
ideal method. Clin Cancer Res. 13:4954–4955. 2007. View Article : Google Scholar : PubMed/NCBI
|
