Correlation of Epidermal Growth Factor Receptor Gene Mutations in Tumor Tissue and Clinical Chemosensitivity in Patients with Advanced Non-Small Cell Lung Cancer
Date Issued
2006
Date
2006
Author(s)
Hsu, Hsin-Hsin
DOI
en-US
Abstract
Based on current available evidences, the mutations in tyrosine kinase domain of epidermal growth factor receptor (EGFR) was significantly associated with clinical responsiveness to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC). Retrospective studies showed that EGFR tyrosine kinase mutation in tumor specimen was as an independent predictive factor of clinical outcomes for TKI treated patients. Patients with mutations would have better clinical response to TKI and longer overall survival in comparison with wild-type patients. The mutation rate was 30 to 42% in Asian patients, higher than Caucasian patients. However, the relationship between clinical responsiveness to chemotherapy and its impact on survival and EGFR mutations was unclear in patients with advanced NSCLC. In this study, we investigated the influence of EGFR mutations in tumor specimens on the clinical outcomes of advanced NSCLC patients who received chemotherapy as 1st or 2nd line treatment.
In total, 86 patients with available tumor specimens were selected from these clinical trials of NSCLC, which conducted at the Department of Oncology, National Taiwan University Hospital. Tumor sequencing in exon 18 through 21 of EGFR, and retrospective collection of clinical data of patients were performed. RESULTS: 34.9% of patients had EGFR mutations. 44.2% of patients had a partial response to chemotherapy. The mutations in subgroups – more frequently found in patients with adenocarcinoma than patients with other histologic types (40.3% vs 13.3%, p=.05), in female than male (39.4% vs 32.1%, p=.49). The mutation rates were 34.9%, 25.9%, 50.0%, respectively in patients who had never smoked, currently smoked, and formerly smoked. The L858R substitution mutation in exon 21 was the most common mutation in 53.3% of all mutations. The in-frame deletions located around E746-A750 in exon 19 were second frequent in 26.7% of all mutations. The response rate to chemotherapy was 40.0% in EGFR mutation-positive subgroup compared to 46.4% in EGFR mutation-negative subgroup (p=.57). The median time-to-progression (TTP) and overall survival (OS) for the patients with EGFR mutations were 4.9 months (95% CI, 3.0-7.2 months), and 19.0 months (95% CI, 14.7-26.1 months), respectively, compared to the median TTP and OS of patients with wild-type (6.9 months, 95% CI, 6.2-8.2 months in TTP; and 22.6 months, 95% CI, 18.9-24.6 months in OS), there were no statistically significant differences in TTP and OS. Therefore, clinical responsiveness to chemotherapy was not associated with EGFR mutations in advanced NSCLC patients.
In comparison with other related researches, our results were consistent with recent report published by Lee et al, but different from the results of researches (Bell and Eberhard et al) in INTACT and TRIBUTE studies. Bell et al showed that EGFR mutated patients treated with chemotherapy alone had a better overall survival compared with mutation negative patients (median OS, 19.4 months vs 9.2 months), but there were only 6.9% of East Asian patients in INTACT study. In our study, both mutated and wild-type advanced NSCLC patients had long survival (median OS, 19.6 and 22.6 months, respectively). Therefore, it was possible that EGFR mutational status was not a good predictive factor in East Asian patients with advanced NSCLC.
Subjects
非小細胞肺癌
化學療法
表皮生長因子受體
基因突變
non-small cell lung cancer,chemotherapy
epidermal growth factor receptor
gene mutation
SDGs
Type
text
File(s)![Thumbnail Image]()
Loading...
Name
ntu-95-R91451013-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):5e39cb6aa0d5250736a27ce691408af7