Clinical usefulness of gefitinib for non-small-cell lung cancer with a double epidermal growth factor receptor mutation
Open accessAbstract
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.
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Patients with compound mutations are associated with improved outcomes among those harboring rare mutations.
“Patients with compound mutations are associated with improved outcomes among those harboring rare mutations [19,20,48,89], although a high level of heterogeneity exists.”
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Cites
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<i>EGFR</i> Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
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<i>MET</i> Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
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Double mutation and gene copy number of EGFR in gefitinib refractory non-small-cell lung cancer
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Russo, A., Franchina, T., Ricciardi, G., Battaglia, A., Picciotto, M., & Adamo, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061431 · Cited by 110 · see citing works
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- Authors
- OIKAWA, T., OHIRA, T., OTANI, K., HAGIWARA, M., KONAKA, C., & IKEDA, N.
- Affiliations
- International University of Health and Welfare Ichikawa Medical Center (JP)
- Tokyo Medical University (JP)
- Venue
- Molecular and Clinical Oncology
- Publisher
- Spandidos Publications
- Published
- 2014-11-10
- Volume
- 3
- Issue
- 2
- Pages
- 329-333
- ISSN
- 2049-9450 (ISSN-L)
- 2049-9469
- PMC
- PMC4360862
- OpenAlex
- W2043625317
- Cited by
- 9
- References
- 14
- Citations by year
- 2023: 1 · 2021: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 2
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Molecular and Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- gefitinib, non-small cell lung cancer, EGFR mutation, exon 19 deletion, MET, hepatocyte growth factor, treatment response, recurrent lung cancer, EGFR tyrosine kinase inhibitors
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