Identification of genetic alterations associated with primary resistance to EGFR-TKIs in advanced non-small-cell lung cancer patients with EGFR sensitive mutations

Fang Wang; Xia-Yao Diao; Xiao Zhang; Qiong Shao; Yan-Fen Feng; Xin An; Hai-Yun Wang

doi:10.1186/s40880-019-0354-z

Cancer Communications

Table 2 Univariate and multivariate associations of EGFR mutation and FISH status, clinicopathological characteristics, and status of other seven genes with PFS and OS in the total of 416 NSCLC patients

From: Identification of genetic alterations associated with primary resistance to EGFR-TKIs in advanced non-small-cell lung cancer patients with EGFR sensitive mutations

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

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