EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION
STATUS AND THE IMPACT ON CLINICAL OUTCOMES
IN PATIENTS WITH NON-SMALL CELL LUNG CANCER
Huang HM1, Wei Y1, Wang JJ1, Ran FY1, Wen Y2, Chen QH3, Zhang BF1,*
*Corresponding Author: Dr. Bingfei Zhang, Sinopharm Dongfeng General Hospital, Hubei University
of Medicine, No. 16 Daling Road, 442008, Shiyan, Hubei, China. Tel.: + 86-29-8272597,
Email: dfzyysszx@163.com
page: 29
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RESULTS
Clinical characteristics
EGFR mutations were significantly more common in
female than in male (57.4% vs 31.5%, p <0.001). Younger
patients (≤ 65years) had a slightly higher mutation rate in
comparison with patients >65years, but there was no statistical
significance (46.2% vs 39.6%, p = 0.308). A higher
frequency of EGFR mutation was observed in non-smokers
versus smokers, and the difference was statistically significant
(56.8% vs 29.7%, p <0.001). In addition, a noticeable
increase of EGFR mutations was found in NSCLC patients
with adenocarcinoma than those with non-adenocarcinoma
(48.3% vs 3.7%, p <0.001) (Table 1).
EGFR mutations
We identified 103 cases with EGFR mutations among
the 238 NSCLC patients, and the total EGFR mutation rate
was 43.3%. A single mutation was found in 102 patients
and 1 patient had multiple exon mutations (19-Del mutation
and T790M mutation). Therefore, a total of 104 mutations
were detected in 103 patients. Exons 19 and 21 were
the highest mutation frequencies, with 20.6% and 19.3%,
respectively. The mutation rate of exon 18 was 2.5% and it
was 0.4% for exon 20. An overview of detected mutations
is shown in Figure 2.
Distribution of exons 18-21
Table 3 shows the distribution of exons 18-21 in 103
EGFR mutation-positive patients. 60.2% of the patients
with mutations were female, and exons 18 and 21 mutations
more commonly occurred in female patients (83.3% and
Table 1. Patient characteristics
Patient characteristics Total N(%) EGFR mutations N (%) Wild type EGFR N (%) P-value
Gender <0.001
Female 108(45.4%) 62(57.4%) 46(42.6%)
Male 130(54.6%) 41(31.5%) 89(68.5%)
Age 0.308
>65 106(44.5%) 42(39.6%) 64(60.4%)
≤65 132(55.5%) 61(46.2%) 71(53.8%)
Smoking history <0.001
Current smoker 58(25.6%) 15(25.9%) 43(74.1%)
Former smoker 37(16.3%) 11(29.7%) 26(70.3%)
Never smoker 132(58.1%) 75(56.8%) 57(43.2%)
Histology types <0.001
Adenocarcinoma 211(88.7%) 102(48.3%) 109(51.7%)
Non-adenocarcinoma 27(11.3%) 1(3.7%) 26(96.3%)
Stage classification 0.990
I-II 74(31.1%) 32(43.2%) 42(56.8%)
IIIA 7(2.9%) 3(42.9%) 4(57.1%)
IIIB 39(16.4%) 16(41.0%) 23(59.0%)
IV 118(49.6%) 52(44.1%) 66(55.9%)
EGFR: epidermal growth factor receptor
Table 2. Mutations detected in exons 18-21 of EGFR
Exon EGFR mutation types
Exon 18 G719A; G719C; G719S
Exon 19 E746_A750del (Cosmic ID:6223); E746_T751>A; E746_S752>V; L747_A750>P; L747_E749del; L747_S752del;
E746_A750del(Cosmic ID:6225); L747_A750>P; L747_P753>S; L747_T751del; L747_T751>P
Exon 20 T790M; S768I; H773_V774insH; D770_N771insG; V769_D770insASV
Exon 21 L858R; L861Q
EGFR: epidermal growth factor receptor
32
EGFR STATUS IN NSCLC PATIENTS
60.9%, respectively). 59.2% of the patients with mutations
were under 65 years of age, and exons 18 and 19 mutations
mostly occurred in younger patients (100.0% and 62.0%,
respectively), however exon 20 mutations mainly occurred
in patients of advanced age (>65 years, 100%). 74.3% of the
patients with mutations were in never smokers and exons
18, 19, and 21 were the major mutant sites (83.3%, 77.1%
and 69.6%, respectively). Patients with adenocarcinoma
accounted for 99.0% of all EGFR mutations.
Independent favorable factors for EGFR mutations
According to the results of univariate analysis, variables
significantly associated with EGFR mutations were
gender (p <0.001), smoking history (p <0.001), and histology
types (p <0.001). Table 4 shows the details. We
defined the EGFR mutation status as a dependent variable,
the statistically significant independent variables in
the univariate analysis were entered into the multivariate
logistic regression analysis. Multivariate logistic regression
identified never smoker (OR = 2.76, 95% CI = 1.04
-7.34, p =0.042) and adenocarcinoma (OR = 17.07, 95%
CI = 2.21-132.04, p =0.007) to be independent favorable
factors for EGFR mutations. When adjusted by smoking
history and histology types, gender was no longer found
to be significant (p = 0.498).
Progression-free survival and overall survival
Figure 3 shows the hazard ratio (HR) for the risk of
progression in 157 advanced NSCLC patients (Stage IIIBIV),
with and without EGFR mutations. The most common
EGFR mutations identified among advanced patients were
19-Del mutation and L858R mutation, comprising 44%
(n=30) and 46% (n=31) of the mutation positive cases,
respectively. The remaining mutations (four G719X, one
L861Q, one 20-Ins, one T790M/19-Del) accounted for
10% (data not shown). Patients with any type of EGFR
mutations were enrolled in analysis of the PFS and OS in
the present study. At the time of analysis, 31 of 68 patients
with EGFR mutations (46%) and 63 of 89 patients with
wild type EGFR (71%) had died. The median follow-up
was 17 months (range 1-52 months). The median PFS was
11 months (95% CI 7.6-14.4) in patients with EGFR mutations
versus 4 months (95% CI 3.0-5.0) in patients with
wild type EGFR (Figure 3A). The median OS in patients
with EGFR mutations was 24 months (95% CI 20.5-27.5),
and it was 12 months (95% CI 8.0-16.0) in patients with
wild type EGFR (Figure 3B). Compared to patients with
EGFR mutations, patients with wild type EGFR had 2.24
times the risk of progression (HR 2.24, 95% CI 1.62-3.10;
p <0.0001) and 2.28 times the risk of death (HR 2.28, 95%
CI 1.52-3.42; p <0.0001).
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