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Clinical usefulness of gefitinib for non-small-cell lung cancer with a double epidermal growth factor receptor
Takefumi Oikawa1, Tatsuo Ohira2, Keishi Otani2
1Chemotherapy Research Institute, Kaken Hospital, Ichikawa, Chiba 272-0827.
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.
Insights
Epidermal growth factor receptor (EGFR) exon 20 mutations in non-small-cell lung cancer (NSCLC) may respond to gefitinib if an additional EGFR mutation is present. This finding impacts targeted therapy selection for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gefitinib is a targeted therapy for non-small-cell lung cancer (NSCLC) that inhibits the epidermal growth factor receptor (EGFR).
- Understanding the specific patterns of EGFR mutations is crucial for predicting treatment response and optimizing gefitinib therapy.
- The role of specific EGFR mutations, particularly exon 20 alterations, in gefitinib sensitivity remains an area of active investigation.
Purpose of the Study:
- To investigate the correlation between epidermal growth factor receptor (EGFR) gene mutation patterns and gefitinib treatment sensitivity in non-small-cell lung cancer (NSCLC).
- To identify potential predictive biomarkers for gefitinib response in NSCLC patients with diverse EGFR mutation profiles.
- To explore the role of co-occurring EGFR mutations and other molecular alterations in non-responders.
Main Methods:
- Analysis of 44 surgically resected non-small-cell lung cancer (NSCLC) specimens from patients treated with gefitinib.
- Detection of EGFR mutations using cycleave PCR technique.
- Immunohistochemical staining for hepatocyte growth factor receptor (HGFR; MET) and hepatocyte growth factor (HGF) in non-responder specimens.
Main Results:
- EGFR mutations identified included exon 18 (1), exon 19 deletion (23), exon 20 (2), exon 21 (16), and combined exon 20 and 21 (2).
- Out of 44 patients, there were 4 non-responders, 25 intermediate responders, and 15 long-term responders.
- Non-responders included the two patients with an exon 20 mutation; three of these non-responder specimens stained positive for MET, and one for HGF.
Conclusions:
- Non-small-cell lung cancer (NSCLC) with an EGFR exon 20 mutation may exhibit sensitivity to gefitinib when an additional EGFR mutation is present.
- The presence of MET or HGF alterations might be associated with resistance to gefitinib in certain NSCLC cases.
- Further research is warranted to elucidate the complex interplay of EGFR mutations and resistance mechanisms in gefitinib therapy for NSCLC.
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