World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 8, Number 6, December 2017, pages 180-187

Neutrophil-to-Lymphocyte Ratio Predicts Overall Survival of Advanced Non-Small Cell Lung Cancer Harboring Mutant Epidermal Growth Factor Receptor

Figure 1. Kaplan-Meier curves of overall survival. (a) Neutrophil-to-lymphocyte ratio (NLR). (b) Lymphocyte-to-monocyte ratio (LMR).

Figure 2. Kaplan-Meier curves of progression-free survival (PFS). (a) Neutrophil-to-lymphocyte ratio (NLR). (b) Lymphocyte-to-monocyte ratio (LMR).

**Table 1.** Comparisons of Backgrounds and Laboratory Data Between Two Groups Divided According to Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratios
Groups	ALL	NLR	LMR
^aMann-Whitney test. ^bFisher’s extract test. ^cDouble mutations. Exon 19del + Exon 21 L858R and Exon 21 L858R + Exon 18 G719S in each one case. Ad: adenocarcinoma; BMI: body mass index; del: deletion; CI: confidence interval; ECOG PS: Eastern Cooperative Oncology Group performance status; LMR: lymphocyte-to-monocyte ratio; Lymph: lymphocyte; met: metastasis; Mono: monocyte; mt: mutation; Neut: neutrophil; NLR: neutrophil-to-lymphocyte ratio; Rec: post-surgical recurrence; SD: standard deviation.
N	152	54	98		105	47
Backgrounds
Age (years, mean ± SD)	70.3 ± 10.3	70.5 ± 8.6	70.2 ± 11.1	0.66^a	70.4 ± 10.7	70.1 ± 9.4	0.69^a
Sex (N, male/female)	57/95	15/39	42/56	0.08^b	45/60	12/35	0.047^b
Histology (N, Ad/others)	148/4	54/0	94/4	0.30^b	101/4	47/0	0.31^b
Stage (N, IIIA/IIIB/IV/Rec)	10/3/102/37	4/2/30/18	6/1/72/19	0.10^b	6/1/74/24	4/2/28/13	0.32^b
Distant met (N)	132	46	86	0.44^b	95	39	0.28^b
Brain met (N)	32	13	19	0.54^b	21	11	0.67^b
Liver met (N)	14	3	11	0.38^b	10	4	1.00^b
Bone met (N)	55	11	44	< 0.01^b	45	10	0.01^b
ECOG PS (N, 0 - 1/2/3/4)	111/32/7/2	49/5/0/0	62/27/7/2	< 0.01^b	68/28/7/2	43/4/0/0	< 0.01^b
BMI (mean ± SD)	21.8 ± 4.1	22.0 ± 3.3	21.6 ± 4.5	0.13^a	21.7 ± 4.4	22.0 ± 3.4	0.30^a
EGFR mt (N)^c
Ex 19del	74	27	47		50	24
Ex 21 point mt	74	25	49		53	21
Minor mt	6	3	3		3	3
Ex19 del vs. other	74/78	27/27	47/51	0.87^b	50/55	24/23	0.73^b
Laboratory data
Neut (cells/µL)	4,183 ± 1,956	3,075 ± 1,095	4,793 ± 2,060	< 0.01^a	4,606 ± 2,093	3,237 ± 1,155	< 0.01^a
Lymph (cells/µL)	1,496 ± 605	1,962 ± 554	1,239 ± 463	< 0.01^a	1,338 ± 507	1,850 ± 659	< 0.01^a
Mono (cells/µL)	411 ± 177	349 ± 123	446 ± 193	< 0.01^a	468 ± 175	286 ± 101	< 0.01^a

Table 1. Comparisons of Backgrounds and Laboratory Data Between Two Groups Divided According to Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratios

Groups

ALL

NLR

LMR

< 2.11

≥ 2.11

< 5.09

≥ 5.09

^aMann-Whitney test. ^bFisher’s extract test. ^cDouble mutations. Exon 19del + Exon 21 L858R and Exon 21 L858R + Exon 18 G719S in each one case. Ad: adenocarcinoma; BMI: body mass index; del: deletion; CI: confidence interval; ECOG PS: Eastern Cooperative Oncology Group performance status; LMR: lymphocyte-to-monocyte ratio; Lymph: lymphocyte; met: metastasis; Mono: monocyte; mt: mutation; Neut: neutrophil; NLR: neutrophil-to-lymphocyte ratio; Rec: post-surgical recurrence; SD: standard deviation.

152

105

Backgrounds

Age (years, mean ± SD)

70.3 ± 10.3

70.5 ± 8.6

70.2 ± 11.1

0.66^a

70.4 ± 10.7

70.1 ± 9.4

0.69^a

Sex (N, male/female)

57/95

15/39

42/56

0.08^b

45/60

12/35

0.047^b

Histology (N, Ad/others)

148/4

54/0

94/4

0.30^b

101/4

47/0

0.31^b

Stage (N, IIIA/IIIB/IV/Rec)

10/3/102/37

4/2/30/18

6/1/72/19

0.10^b

6/1/74/24

4/2/28/13

0.32^b

Distant met (N)

132

0.44^b

0.28^b

Brain met (N)

0.54^b

0.67^b

Liver met (N)

0.38^b

1.00^b

Bone met (N)

< 0.01^b

0.01^b

ECOG PS (N, 0 - 1/2/3/4)

111/32/7/2

49/5/0/0

62/27/7/2

< 0.01^b

68/28/7/2

43/4/0/0

< 0.01^b

BMI (mean ± SD)

21.8 ± 4.1

22.0 ± 3.3

21.6 ± 4.5

0.13^a

21.7 ± 4.4

22.0 ± 3.4

0.30^a

EGFR mt (N)^c

Ex 19del

Ex 21 point mt

Minor mt

Ex19 del vs. other

74/78

27/27

47/51

0.87^b

50/55

24/23

0.73^b

Laboratory data

Neut (cells/µL)

4,183 ± 1,956

3,075 ± 1,095

4,793 ± 2,060

< 0.01^a

4,606 ± 2,093

3,237 ± 1,155

< 0.01^a

Lymph (cells/µL)

1,496 ± 605

1,962 ± 554

1,239 ± 463

< 0.01^a

1,338 ± 507

1,850 ± 659

< 0.01^a

Mono (cells/µL)

411 ± 177

349 ± 123

446 ± 193

< 0.01^a

468 ± 175

286 ± 101

< 0.01^a

**Table 2.** Treatment and Outcomes
Group	All	NLR	LMR
^aFisher’s extract test. Afa: afatinib; CI: confidence interval; DCR: disease control rate; Erl: erlotinib; Gef: gefitinib; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; RR: response rate; TKI: tyrosine kinase inhibitor; TRT: thoracic radiotherapy.
N	152	54	98		105	47
TKI choice (N, Gef/Erl/Afa)	107/36/9	43/10/1	64/26/8	0.12	72/27/6	35/9/3	0.68
TKI line (N, first/second/≥ third)	104/38/11	37/14/4	67/24/7	1.00	71/27/7	33/11/3	0.96
Pre TKI treatment (N)	49	18	31	0.86	34	10	0.18
Platinum-based	39	14	25	1.00	30	7	0.10
Curative-intent TRT	8	3	5	1.00	6	2	1.00
Post TKI treatment (N)	98	41	57	0.03	64	34	0.20
Cytotoxic drugs	62	26	36	0.23	40	22	0.37
Platinum-based	27	10	17	1.00	18	13	0.19
Osimertinib	14	5	9	1.00	9	5	0.76
Re-challenge of TKI	62	27	35	0.12	42	22	0.48
Palliative radiotherapy (N)	57	18	39	0.49	38	19	0.72
TKI Response (N)
Complete response	5	3	2		2	3
Partial response	88	36	52		55	33
Stable disease	29	11	18		21	8
Progressive disease	19	2	17		18	1
Not evaluated	11	2	9		9	2
RR (%) (95% CI)	61.2 (53.0 - 69.0)	72.2 (58.4 - 83.5)	55.1 (44.7 - 65.2)	0.055	54.3 (44.3 - 64.0)	76.6 (62.0 - 87.7)	0.01
DCR (%) (95% CI)	80.3 (73.0 - 86.3)	92.6 (82.1- 97.9)	73.5 (63.6 - 81.9)	< 0.01	74.3 (64.8 - 82.3)	93.6 (82.5 - 98.7)	< 0.01

Table 2. Treatment and Outcomes

Group

All

NLR

LMR

< 2.11

≥ 2.11

P^a

< 5.09

≥ 5.09

P^a

^aFisher’s extract test. Afa: afatinib; CI: confidence interval; DCR: disease control rate; Erl: erlotinib; Gef: gefitinib; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; RR: response rate; TKI: tyrosine kinase inhibitor; TRT: thoracic radiotherapy.

152

105

TKI choice (N, Gef/Erl/Afa)

107/36/9

43/10/1

64/26/8

0.12

72/27/6

35/9/3

0.68

TKI line (N, first/second/≥ third)

104/38/11

37/14/4

67/24/7

1.00

71/27/7

33/11/3

0.96

Pre TKI treatment (N)

0.86

0.18

Platinum-based

1.00

0.10

Curative-intent TRT

1.00

Post TKI treatment (N)

0.03

0.20

Cytotoxic drugs

0.23

0.37

Platinum-based

1.00

0.19

Osimertinib

1.00

0.76

Re-challenge of TKI

0.12

0.48

Palliative radiotherapy (N)

0.49

0.72

TKI Response (N)

Complete response

Partial response

Stable disease

Progressive disease

Not evaluated

RR (%) (95% CI)

61.2 (53.0 - 69.0)

72.2 (58.4 - 83.5)

55.1 (44.7 - 65.2)

0.055

54.3 (44.3 - 64.0)

76.6 (62.0 - 87.7)

0.01

DCR (%) (95% CI)

80.3 (73.0 - 86.3)

92.6 (82.1- 97.9)

73.5 (63.6 - 81.9)

< 0.01

74.3 (64.8 - 82.3)

93.6 (82.5 - 98.7)

< 0.01

**Table 3.** Univariate Cox Hazard Analyses of Factors Associated With Overall Survival and Progression-Free Survival
	OS	PFS
Afa: afatinib; BMI: body mass index; Ccr: creatinine clearance; CI: confidence interval; CRP: C-reactive protein; del: deletion; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor- tyrosine kinase inhibitor; Erl: erlotinib; Gef: gefinitib; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression-free survival.
Age (years < 75 vs. ≥ 75)	1.18	0.75 - 1.85	0.48	0.97	0.67 - 1.41	0.88
Sex (female vs. male)	1.33	0.86 - 2.07	0.19	1.17	0.81 - 1.68	0.41
Distant metastasis (no vs. yes)	2.08	0.99 - 4.38	0.054	2.10	1.12 - 3.93	0.02
ECOG PS (0 - 1 vs. 2 - 4)	4.08	2.56 - 6.50	< 0.01	1.98	1.33 - 2.93	< 0.01
BMI (≥ 18.5 vs. < 18.5)	1.58	0.95 - 2.64	0.08	1.60	1.04 - 2.47	0.03
EGFR mutation (exon 19 del vs. others)	1.27	0.82 - 1.95	0.29	1.14	0.79 - 1.63	0.49
EGFR-TKI line (first vs. second or later)	1.46	0.94 - 2.26	0.09	1.47	1.01 - 2.15	0.04
EGFR-TKI (Gef vs. Erl or Afa)	0.84	0.50 - 1.41	0.51	0.61	0.40 - 0.92	0.02
Hemoglobin (g/dL)	0.89	0.77 - 1.02	0.09	0.94	0.85 - 1.05	0.29
Ccr (mL/min) (/10)	0.86	0.74 - 0.998	0.047	0.88	0.78 - 0.99	0.04
Sodium (mEq/L) (/10)	0.19	0.10 - 0.39	< 0.01	0.34	0.19 - 0.62	< 0.01
LDH (IU/L) (/100)	1.36	1.19 - 1.54	< 0.01	1.24	1.11 - 1.39	< 0.01
CRP (mg/dL)	1.17	1.08 - 1.27	< 0.01	1.19	1.10 - 1.29	< 0.01
NLR	1.12	1.07 - 1.18	< 0.01	1.08	1.03 - 1.13	< 0.01
LMR	0.78	0.69 - 0.89	< 0.01	0.89	0.81 - 0.98	0.02

Table 3. Univariate Cox Hazard Analyses of Factors Associated With Overall Survival and Progression-Free Survival

PFS

95% CI

Afa: afatinib; BMI: body mass index; Ccr: creatinine clearance; CI: confidence interval; CRP: C-reactive protein; del: deletion; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor- tyrosine kinase inhibitor; Erl: erlotinib; Gef: gefinitib; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression-free survival.

Age (years < 75 vs. ≥ 75)

1.18

0.75 - 1.85

0.48

0.97

0.67 - 1.41

0.88

Sex (female vs. male)

1.33

0.86 - 2.07

0.19

1.17

0.81 - 1.68

0.41

Distant metastasis (no vs. yes)

2.08

0.99 - 4.38

0.054

2.10

1.12 - 3.93

0.02

ECOG PS (0 - 1 vs. 2 - 4)

4.08

2.56 - 6.50

< 0.01

1.98

1.33 - 2.93

< 0.01

BMI (≥ 18.5 vs. < 18.5)

1.58

0.95 - 2.64

0.08

1.60

1.04 - 2.47

0.03

EGFR mutation (exon 19 del vs. others)

1.27

0.82 - 1.95

0.29

1.14

0.79 - 1.63

0.49

EGFR-TKI line (first vs. second or later)

1.46

0.94 - 2.26

0.09

1.47

1.01 - 2.15

0.04

EGFR-TKI (Gef vs. Erl or Afa)

0.84

0.50 - 1.41

0.51

0.61

0.40 - 0.92

0.02

Hemoglobin (g/dL)

0.89

0.77 - 1.02

0.09

0.94

0.85 - 1.05

0.29

Ccr (mL/min) (/10)

0.86

0.74 - 0.998

0.047

0.88

0.78 - 0.99

0.04

Sodium (mEq/L) (/10)

0.19

0.10 - 0.39

< 0.01

0.34

0.19 - 0.62

< 0.01

LDH (IU/L) (/100)

1.36

1.19 - 1.54

< 0.01

1.24

1.11 - 1.39

< 0.01

CRP (mg/dL)

1.17

1.08 - 1.27

< 0.01

1.19

1.10 - 1.29

< 0.01

NLR

1.12

1.07 - 1.18

< 0.01

1.08

1.03 - 1.13

< 0.01

LMR

0.78

0.69 - 0.89

< 0.01

0.89

0.81 - 0.98

0.02

**Table 4.** Multivariate Cox Hazard Analyses of Factors Associated With Overall Survival
	NLR	LMR
BMI: body mass index; Ccr: creatinine clearance: CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitors; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio.
Distant metastasis (no vs. yes)	1.59	0.73 - 3.50	0.25	1.44	0.64 - 3.24	0.38
ECOG PS (0 - 1 vs. 2 - 4)	3.46	2.03 - 5.89	< 0.01	3.41	1.99 - 5.82	< 0.01
BMI (≥ 18.5 vs. < 18.5)	1.62	0.89 - 2.93	0.12	1.58	0.87 - 2.87	0.14
EGFR-TKI line (first vs. second or later)	1.71.	1.07 - 2.73	0.02	1.72	1.08 - 2.74	0.02
Hemoglobin (g/dL)	1.14	0.97 - 1.34	0.11	1.15	0.98 - 1.36	0.08
Ccr (mL/min) (/10)	0.86	0.73 - 1.02	0.08	0.86	0.73 - 1.01	0.07
Sodium (mEq/L) (/10)	0.30	0.13 - 0.71	< 0.01	0.27	0.11 - 0.64	< 0.01
LDH (IU/L) (/100)	1.24	1.05 - 1.48	0.01	1.27	1.07 - 1.50	< 0.01
CRP (mg/dL)	1.01	0.90 - 1.14	0.82	0.98	0.86 - 1.11	0.74
NLR	1.07	1.01 - 1.14	0.03	-	-	-
LMR	-	-	-	0.88	0.76 - 1.01	0.07

Table 4. Multivariate Cox Hazard Analyses of Factors Associated With Overall Survival

NLR

LMR

95% CI

BMI: body mass index; Ccr: creatinine clearance: CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitors; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio.

Distant metastasis (no vs. yes)

1.59

0.73 - 3.50

0.25

1.44

0.64 - 3.24

0.38

ECOG PS (0 - 1 vs. 2 - 4)

3.46

2.03 - 5.89

< 0.01

3.41

1.99 - 5.82

< 0.01

BMI (≥ 18.5 vs. < 18.5)

1.62

0.89 - 2.93

0.12

1.58

0.87 - 2.87

0.14

EGFR-TKI line (first vs. second or later)

1.71.

1.07 - 2.73

0.02

1.72

1.08 - 2.74

0.02

Hemoglobin (g/dL)

1.14

0.97 - 1.34

0.11

1.15

0.98 - 1.36

0.08

Ccr (mL/min) (/10)

0.86

0.73 - 1.02

0.08

0.86

0.73 - 1.01

0.07

Sodium (mEq/L) (/10)

0.30

0.13 - 0.71

< 0.01

0.27

0.11 - 0.64

< 0.01

LDH (IU/L) (/100)

1.24

1.05 - 1.48

0.01

1.27

1.07 - 1.50

< 0.01

CRP (mg/dL)

1.01

0.90 - 1.14

0.82

0.98

0.86 - 1.11

0.74

NLR

1.07

1.01 - 1.14

0.03

LMR

0.88

0.76 - 1.01

0.07

**Table 5.** Multivariate Cox Hazard Analyses of Factors Associated With Progression-Free Survival
	NLR	LMR
Afa: afatinib; ALP: alkaline phosphatase; BMI: body mass index; Ccr: creatinine clearance; CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitors; Erl: erlotinib; Gef: gefitinib; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio.
Distant metastasis (no vs. yes)	1.69	0.87 - 3.27	0.12	1.77	0.92 - 3.42	0.09
ECOG PS (0 - 1 vs. 2 - 4)	1.55	0.97 - 2.47	0.07	1.63	1.01 - 2.61	0.04
BMI (≥ 18.5 vs. < 18.5)	1.53	0.94 - 2.47	0.09	1.57	0.96 - 2.55	0.07
EGFR-TKI line (first vs. second or later)	1.47	0.99 - 2.19	0.058	1.49	1.00 - 2.23	0.049
EGFR-TKI (Gef vs. Erl or Afa)	0.63	0.40 - 0.99	0.046	0.64	0.41 - 1.01	0.06
Ccr (mL/min) (/10)	0.94	0.82 - 1.08	0.37	0.94	0.82 - 1.07	0.36
Sodium (mEq/L) (/10)	0.60	0.30 - 1.20	0.15	0.60	0.30 - 1.21	0.16
LDH (IU/L) (/100)	1.11	0.97 - 1.27	0.15	1.12	0.98 - 1.29	0.10
CRP (mg/dL)	1.10	0.99 - 1.22	0.08	1.10	0.99 - 1.23	0.07
NLR	1.03	0.97 - 1.10	0.29	-	-	-
LMR	-	-	-	1.00	0.90 - 1.12	0.99

Table 5. Multivariate Cox Hazard Analyses of Factors Associated With Progression-Free Survival

NLR

LMR

95% CI

Afa: afatinib; ALP: alkaline phosphatase; BMI: body mass index; Ccr: creatinine clearance; CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitors; Erl: erlotinib; Gef: gefitinib; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio.

Distant metastasis (no vs. yes)

1.69

0.87 - 3.27

0.12

1.77

0.92 - 3.42

0.09

ECOG PS (0 - 1 vs. 2 - 4)

1.55

0.97 - 2.47

0.07

1.63

1.01 - 2.61

0.04

BMI (≥ 18.5 vs. < 18.5)

1.53

0.94 - 2.47

0.09

1.57

0.96 - 2.55

0.07

EGFR-TKI line (first vs. second or later)

1.47

0.99 - 2.19

0.058

1.49

1.00 - 2.23

0.049

EGFR-TKI (Gef vs. Erl or Afa)

0.63

0.40 - 0.99

0.046

0.64

0.41 - 1.01

0.06

Ccr (mL/min) (/10)

0.94

0.82 - 1.08

0.37

0.94

0.82 - 1.07

0.36

Sodium (mEq/L) (/10)

0.60

0.30 - 1.20

0.15

0.60

0.30 - 1.21

0.16

LDH (IU/L) (/100)

1.11

0.97 - 1.27

0.15

1.12

0.98 - 1.29

0.10

CRP (mg/dL)

1.10

0.99 - 1.22

0.08

1.10

0.99 - 1.23

0.07

NLR

1.03

0.97 - 1.10

0.29

LMR

1.00

0.90 - 1.12

0.99

**Table 6.** Review of Previous Studies of Multivariate Analyses for Prediction of Survival Outcomes in Patients With EGFR Mutant NSCLC
Author (year)	Country	N	Treatment	Variable	Multivariate analyses
CI: confidence interval; Erl: erlotinib; Gef: gefitinib; HR: hazard ratio; NA: not assessed; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression free survival.
Lin et al [27] (2014)	China	81	Gef (30%) Erl (70%) All first-line	NLR	3.5	3.29 (1.62 - 6.71)	< 0.001	3.89 (1.98 - 7.68)	< 0.001
Chen et al [30] (2015)	Taiwan	253	All first-line	LMR	3.29	2.36 (1.66 - 3.35)	< 0.001	1.71 (1.14 - 2.56)	0.009
Sim et al [29] (2016)	Korea	85	All first-line	NLR	3	NA	NA	1.239 (0.693 - 2.215)	0.469
Meriggi et al [28] (2017)	Italy	63	Gef (71%) Erl (29%)	NLR	3.5	2.699 (1.187 - 6.137)	0.018	2.275 (1.257 - 4.116)	0.007
Ding et al [26] (2017)	Australia	85	First-line (85%)	NLR	5	0.43 (0.19 - 0.94)	0.04	0.40 (0.18 - 0.87)	0.02
Ours	Japan	152	Gef (70%) Erl (24%) First-line (68%)	NLR	-	1.07 (1.01 - 1.14)	0.03	1.03 (0.97 - 1.10)	0.29
				LMR	-	0.88 (0.76 - 1.01)	0.07	1.00 (0.90 - 1.12)	0.99

Table 6. Review of Previous Studies of Multivariate Analyses for Prediction of Survival Outcomes in Patients With EGFR Mutant NSCLC

Author (year)

Country

Treatment

Variable

Multivariate analyses

Cut-off

PFS

HR (95% CI)

CI: confidence interval; Erl: erlotinib; Gef: gefitinib; HR: hazard ratio; NA: not assessed; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression free survival.

Lin et al [27] (2014)

China

Gef (30%) Erl (70%) All first-line

NLR

3.5

3.29 (1.62 - 6.71)

< 0.001

3.89 (1.98 - 7.68)

< 0.001

Chen et al [30] (2015)

Taiwan

253

All first-line

LMR

3.29

2.36 (1.66 - 3.35)

< 0.001

1.71 (1.14 - 2.56)

0.009

Sim et al [29] (2016)

Korea

All first-line

NLR

1.239 (0.693 - 2.215)

0.469

Meriggi et al [28] (2017)

Italy

Gef (71%) Erl (29%)

NLR

3.5

2.699 (1.187 - 6.137)

0.018

2.275 (1.257 - 4.116)

0.007

Ding et al [26] (2017)

Australia

First-line (85%)

NLR

0.43 (0.19 - 0.94)

0.04

0.40 (0.18 - 0.87)

0.02

Ours

Japan

152

Gef (70%) Erl (24%) First-line (68%)

NLR

1.07 (1.01 - 1.14)

0.03

1.03 (0.97 - 1.10)

0.29

LMR

0.88 (0.76 - 1.01)

0.07

1.00 (0.90 - 1.12)

0.99