Background
Methods
Patients and clinical features
Before Gefitinib treatments
|
At Gefitinib treatment failure
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Case No
b
|
Smoking
|
Staging
|
Gefitinib response
|
EGFR mutation type
|
MET FISH status
|
MET IHC
|
EGFR mutation type
|
MET FISH status
|
PFS(Months)
|
OS(Months)
|
1 | - | IV | PR |
Ex19 deletion
|
++
|
+
|
Ex19 deletion
|
++
|
7.3
| 15 |
2 | - | IV | PR |
Ex19 deletion
|
+
| Not detected |
+
|
7.6
|
11.9
| |
3 | + | Relapse | PR |
Ex19 deletion
|
+
|
Ex19 deletion/T790M
|
+
|
18.5
|
34.4
| |
4 | - | Relapse | PR |
Ex19 deletion
|
+
|
-
|
16.6
|
20.9
| ||
5 | + | IIIA | PR |
Ex19 deletion
|
+
|
8.5
| 20 | |||
6 | - | Relapse | PR |
Ex19 deletion
|
+
| 1.8 | 1.8 | |||
7 | - | IV | PD |
L858R
|
+
|
L858R
|
+
|
13.6
|
15
| |
8 | + | Relapse | PD |
L858R
|
+
|
+
|
2.7
|
8.8
| ||
9 | - | Relapse | CR |
L858R
|
+
|
-
|
13
| 28.4 | ||
10 | - | Relapse | PR |
L858R
|
+
|
-
| 7.6 | 11.2 | ||
11 | + | IV | PR |
L858R
|
+
|
5.7
| 7.3 | |||
12 | + | IV | PR |
Ex19 deletion
|
-
|
Ex19 deletion
|
-
|
13.9
| 21 | |
13 | + | IV | PR |
Ex19 deletion
|
-
|
Ex19 deletion
|
-
|
10.4
| 36.4 | |
14 | - | IV | PR |
Ex19 deletion
|
-
|
Ex19 deletion
|
-
|
24.7
|
31.1
| |
15 | - | Relapse | PR |
Ex19 deletion
|
-
| - |
Ex19 deletion/T790M
| - |
28.4
| 33.8 |
16 | - | Relapse | PR |
Ex19 deletion
|
-
| - |
11.1
|
21
| ||
17 | + | Relapse | PR |
Ex19 deletion
|
-
| - |
24.4
| 24.4 | ||
18 | - | IIIA | PR |
Ex19 deletion
|
-
| 6.5 | 14.9 | |||
19 | - | IIIB | PR |
Ex19 deletion
|
-
| 29.8 | 38.2 | |||
20 | + | IIIB | PR |
Ex19 deletion
|
-
|
41.5
|
48.6
| |||
21 | - | IV | PR |
Ex19 deletion
|
-
| 13.2 | 26.7 | |||
22 | + | IV | PR |
Ex19 deletion
|
-
| 17.1 | 17.1 | |||
23 | - | IV | PR |
Ex19 deletion
|
-
|
13.3
|
19.2
| |||
24 | - | IV | PR |
Ex19 deletion
|
-
| 21.8 | 25.5 | |||
25 | - | IV | PR |
Ex19 deletion
|
-
|
15.2
| 31.6 | |||
26 | - | IV | SD |
Ex19 deletion
|
-
|
3.4
|
26.8
| |||
27 | + | Relapse | PR |
Ex19 deletion
|
-
|
18.7
| 50.2 | |||
28 | + | Relapse | PR |
Ex19 deletion
|
-
| 15.9 | 20.2 | |||
29 | - | Relapse | PR |
Ex19 deletion
|
-
|
12.1
|
15
| |||
30 | + | Relapse | SD |
Ex19 deletion
|
-
|
11.1
|
13.6
| |||
31 | - | Relapse | PR |
L858R
|
-
|
L858R
| - |
58.7
| 123.5 | |
32 | - | IV | PR |
L858R
|
-
|
-
| 4.5 | 4.5 | ||
33 | + | Relapse | PR |
L858R
|
-
|
15.5
|
16.7
| |||
34 | + | Relapse | PR |
L858R
|
-
| 13.5 | 13.5 | |||
35 | - | Relapse | PR |
L858R
|
-
| 7.1 | 7.1 |
EGFR mutation analysis
Fluorescence in situ hybridization (FISH)
Immunohistochemical (IHC) analysis
Statistical analyses
Results
Status of EGFR and MET genes before gefitinib therapy and at treatment failure
MET gene FISH status
| |||||||
---|---|---|---|---|---|---|---|
FISH-negative
|
FISH-positive
|
p-value
| |||||
Total
|
%
|
Total
|
%
|
Total
|
%
| ||
Variables
| 35 | 100 | 24 | 100 | 11a
| 100 | |
Age
| |||||||
<65 | 13 | 37 | 9 | 38 | 4 | 36 | |
65≦ | 22 | 63 | 15 | 63 | 7 | 64 | 1.00 |
Gender
| |||||||
Male | 15 | 43 | 12 | 50 | 3 | 27 | |
Female | 20 | 57 | 12 | 50 | 8 | 73 | 0.28 |
Smoking status
| |||||||
Current and former smoker | 14 | 40 | 10 | 42 | 4 | 36 | |
Never smoker | 21 | 60 | 14 | 58 | 7 | 63 | 1.00 |
Stage
| |||||||
III | 4 | 11 | 3 | 13 | 1 | 9 | |
IV + Relapse | 31 | 89 | 21 | 87 | 10 | 91 | 1.00 |
EGFR mutation subtype
| |||||||
Exon19 deletion | 25 | 71 | 19 | 79 | 6 | 55 | |
Exon21 L858R
| 10 | 29 | 5 | 21 | 5 | 46 | 0.23 |
Response to Gefitinib
| |||||||
CR + PR | 31 | 89 | 22 | 92 | 9 | 82 | |
SD + PD | 4 | 11 | 2 | 8 | 2 | 18 | 0.57 |
Relationship between GCNs and MET protein expression
Correlation between EGFR gene and gefitinib sensitivity
Correlation between MET gene status, EGFR-TKI sensitivity, PFS and OS after gefitinib treatment
Hazard ratios for death in according to prognostic factors
| ||||
---|---|---|---|---|
Characteristics
|
Comparison
|
Hazard ratio [95% CI
a
]
|
P value
b
| |
Age
| <65 yr vs. ≥65 yr | 1.26 | [0.50-3.17] | 0.62 |
Gender
| Female vs. Male | 0.59 | [0.23-1.49] | 0.27 |
Smoking status
| Never smoker vs. Ever smoker | 0.41 | [0.15-1.13] | 0.08 |
Stage
| III vs. IV/Relapse | 1.46 | [ 0.34-6.37] | 0.61 |
EGFR mutation type
| Exon19 deletion vs. Exon 21 L858R | 1.90 | [0.72-5.00] | 0.62 |
MET FISH
| Negative vs. Positive | 2.25 | [1.07-4.74] |
0.03
|
Hazard ratios for progression in according to prognostic factors
| ||||
Characteristics
|
Comparison
|
Hazard ratio [95% CI
a
]
|
P value
b
| |
Age
| <65 yr vs. ≥65 yr | 0.52 | [0.23-1.15] | 0.11 |
Gender
| Female vs. Male | 0.88 | [0.40-1.93] | 0.75 |
Smoking stutus
| Never smoker vs. Ever smoker | 1.11 | [0.51-2.42] | 0.79 |
Stage
| III vs. IV/Relapse | 1.04 | [0.30-3.64] | 0.95 |
EGFR mutation type
| Exon19 deletion vs. Exon 21 L858R | 1.15 | [0.45-2.91] | 0.77 |
MET FISH
| Negative vs. Positive | 3.83 | [1.75-8.38] |
0.0008
|