Variable
|
PFS
|
OS
|
---|
Univariate
|
Multivariate
|
Univariate
|
Multivariate
|
---|
HR
|
95% CI
|
P
|
HR
|
95% CI
|
P
|
HR
|
95% CI
|
P
|
HR
|
95% CI
|
P
|
---|
Age
|
≤ 60
|
1
| | | | | |
1
| | | | | |
> 60
|
1.01
|
0.82–1.25
|
0.913
| | | |
1.21
|
0.94–1.57
|
0.145
| | | |
Gender
|
Male
|
1
| | |
1
| | |
1
| | |
1
| | |
Female
|
0.59
|
0.48–0.73
|
< 0.001
|
0.56
|
0.42–0.74
|
< 0.001
|
0.59
|
0.45–0.76
|
< 0.001
|
0.65
|
0.48–0.94
|
0.006
|
Smoking status
|
Smoking
|
1
| | |
1
| | |
1
| | |
1
| | |
No smoking
|
0.60
|
0.48–0.74
|
< 0.001
|
0.64
|
0.50–0.81
|
< 0.001
|
0.62
|
0.48–0.80
|
< 0.001
|
0.79
|
0.58–1.06
|
0.113
|
Histology
|
Non-ADC
|
1
| | |
1
| | |
1
| | | | | |
ADC
|
0.67
|
0.52–0.86
|
0.002
|
0.84
|
0.64–1.10
|
0.203
|
0.78
|
0.58–1.07
|
0.122
| | | |
Differentiation
|
High to medium
|
1
| | |
1
| | |
1
| | | | | |
Low
|
1.36
|
1.11–1.68
|
0.004
|
0.89
|
0.72–1.18
|
0.299
|
1.12
|
0.87–1.44
|
0.363
| | | |
Stage
|
Recurrent
|
1
| | | | | |
1
| | | | | |
IIIB and IV
|
0.88
|
0.70–1.10
|
0.254
| | | |
0.83
|
0.63–1.09
|
0.183
| | | |
Line of TKI therapy
|
2, 3
|
1
| | |
1
| | |
1
| | |
1
| | |
1
|
0.68
|
0.53–0.87
|
0.002
|
0.75
|
0.58–0.97
|
0.027
|
0.67
|
0.50–0.90
|
0.009
|
0.78
|
0.57–1.05
|
0.103
|
ECOG PS
|
2
|
1
| | |
1
| | |
1
| | |
1
| | |
0, 1
|
0.71
|
0.52–0.95
|
0.023
|
0.73
|
0.54–0.99
|
0.043
|
1.71
|
1.17–2.48
|
0.004
|
0.62
|
0.43–0.90
|
0.011
|
EGFR mutation
|
Mt
|
1
| | |
1
| | |
1
| | |
1
| | |
Wt
|
0.38
|
0.31–0.47
|
< 0.001
|
0.54
|
0.42–0.70
|
< 0.001
|
0.50
|
0.38–0.65
|
< 0.001
|
0.63
|
0.47–0.85
|
0.002
|
EGFR copy number
|
FISH−
|
1
| | |
1
| | |
1
| | |
1
| | |
FISH+
|
0.54
|
0.43–0.67
|
< 0.001
|
0.67
|
0.54–0.84
|
0.001
|
0.60
|
0.46–0.78
|
< 0.001
|
0.77
|
0.58–1.02
|
0.068
|
ALK
|
Wt
|
1
| | |
1
| | |
1
| | |
1
| | |
Apart
|
2.06
|
1.41–3.02
|
< 0.001
|
1.41
|
0.93–2.16
|
0.105
|
1.59
|
1.00–2.51
|
0.047
|
1.34
|
0.82–2.17
|
0.240
|
BIM
|
Wt
|
1
| | | | | |
1
| | | | | |
Deletion
|
0.89
|
0.58–1.36
|
0.596
| | | |
1.05
|
0.64–1.71
|
0.856
| | | |
KRAS mutation
|
Wt
|
1
| | |
1
| | |
1
| | | | | |
Mt
|
1.99
|
1.33–2.99
|
0.001
|
1.21
|
0.79–1.84
|
0.386
|
1.55
|
0.97–2.47
|
0.070
| | | |
PIK3CA mutation
|
wt
|
1
| | | | | |
1
| | | | | |
mt
|
1.18
|
0.61–2.29
|
0.619
| | | |
1.22
|
0.60–2.47
|
0.583
| | | |
PTEN copy number
|
Intact
|
1
| | | | | |
1
| | | | | |
Deletion
|
1.54
|
0.99–2.39
|
0.058
| | | |
1.06
|
0.64–1.77
|
0.811
| | | |
PTEN expression
|
Normal
|
1
| | |
1
| | |
1
| | | | | |
Low expression
|
1.37
|
1.08–1.74
|
0.011
|
1.10
|
0.86–1.42
|
0.439
|
1.12
|
0.84–1.50
|
0.448
| | | |
MET copy number
|
FISH−
|
1
| | |
1
| | |
1
| | |
1
| | |
FISH+
|
1.87
|
1.35–2.60
|
< 0.001
|
1.51
|
1.07–2.13
|
0.019
|
1.64
|
1.14–2.37
|
0.008
|
1.47
|
1.01–2.13
|
0.045
|
MET expression
|
MAb−
|
1
| | | | | |
1
| | | | | |
MAb+
|
1.01
|
0.79–1.28
|
0.955
| | | |
1.18
|
0.87–1.59
|
0.283
| | | |
MET expression
|
H-score−
|
1
| | | | | |
1
| | | | | |
H-score+
|
1.14
|
0.93–1.40
|
0.217
| | | |
0.97
|
0.75–1.25
|
0.805
| | | |
IGF1R copy number
|
FISH−
|
1
| | |
1
| | |
1
| | | | | |
FISH+
|
1.40
|
1.05–1.87
|
0.019
|
1.07
|
0.78–1.46
|
0.688
|
1.10
|
0.77–1.57
|
0.619
| | | |
IGF1R expression
|
IHC−
|
1
| | | | | |
1
| | | | | |
IHC+
|
1.26
|
0.99–1.61
|
0.062
| | | |
1.05
|
0.78–1.40
|
0.770
| | | |
- ADC adenocarcinoma, ECOG Eastern cooperative oncology group, TKI tyrosine kinase inhibitors, FISH fluorescent in situ hybridization, HR hazard ratio, CI confidence interval, PFS progression-free survival, OS overall survival