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 10, Number 2, April 2019, pages 90-100

Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Biomarkers of Immune-Checkpoint Inhibitor for Non-Small Cell Lung Cancer

Figure 1. Kaplan-Meier curves of overall survival (a, c) and progression-free survival (b, d) of all patients (a, b) and patients without EGFR mutation or ALK rearrangement (c, d) according to GRIm-Score.

Figure 2. Kaplan-Meier curves of overall survival (a, c) and progression-free survival (b, d) of all patients (a, b) and patients without EGFR mutation or ALK rearrangement (c, d) according to RMH score.

Figure 3. Kaplan-Meier curves of overall survival according to albumin (a), LDH (b), NLR (c), and number of metastatic sites (d).

Figure 4. Kaplan-Meier curves of progression-free survival according to albumin (a), LDH (b), NLR (c), and number of metastatic sites (d).

**Table 1.** Baseline Characteristics, Treatment, and Laboratory Data According to GRIm-Score (N = 76)
N	GRIm-Score	P
^aFisher’s exact test, ^bMann-Whitney U test. BMI: body mass index; CI: confidence interval; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; GRIm-Score: Gustave Roussy Immune Score; IQR: interquartile range; ICI: immune-checkpoint inhibitor; LDH: lactate dehydrogenase; NA: not assessed; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; SQ; squamous cell carcinoma; TKI: tyrosine kinase inhibitor; ULN: upper limit of normal.
Backgrounds
Sex (N)
Male/female	35/20	14/7	1.00^a
Age (years)
Median (IQR)	69 (62.5 - 73)	71 (68 - 75)	0.29^b
Smoking status (N)
NS/Ex, CS	12/43	4/17	1.00^a
BMI
Median (IQR)	22.7 (21.0 - 25.1)	22.5 (18.2 - 24.0)	0.26^b
≥ 18.5/< 18.5 (N)	48/7	14/7	0.051^a
Histology (N)
Non-SQ/SQ	42/13	16/5	1.00^a
EGFR mutation (N)
(-) or NA/(+)	46/9	19/2	0.72^a
PD-L1 status (N)
≥ 50%/1-49%/< 1% /NA	13/9/5/28	1/5/3/11	0.25^a
ECOG-PS (N)
0-1/2/3	43/11/1	11/6/4	0.02^a
Metastatic sites (N)
< 3/≥ 3	25/30	10/11	1.00^a
Treatment
ICI regimen (N)
Nivolumab	41	17
Pembrolizumab	11	2
Atezolizumab	3	2	0.08^a
Previous treatment (N)
Anti-angiogenic drug	25	11	0.62^a
EGFR-TKIs	13	2	0.21^a
Radiotherapy	13	6	0.77^a
Further line treatment (N)	31	9	0.32^a
ICI efficacy
ORR (%) (95% CI)	18.2 (9.1 - 30.9)	4.8 (0.1 - 23.8)	0.27^a
DCR (%) (95% CI)	41.8 (28.7 - 55.9)	19.0 (5.4 - 41.9)	0.11^a
Laboratory data
NLR
Median (IQR)	2.64 (1.89 - 3.89)	5.85 (3.57 - 7.18)	< 0.01^b
> 6 (N)	1	10	< 0.01^a
LDH (U/L)
Median (IQR)	208 (184.5 - 242.5)	324 (228 - 387)	< 0.01^b
> ULN (N)	19	16	< 0.01^a
Albumin (g/dL)
Median (IQR)	3.8 (3.5 - 4.0)	3.1 (2.8 - 3.2)	< 0.01^b
< 3.5 g/dL (N)	9	21	< 0.01^a

Table 1. Baseline Characteristics, Treatment, and Laboratory Data According to GRIm-Score (N = 76)

GRIm-Score

Low (N = 55)

High (N = 21)

^aFisher’s exact test, ^bMann-Whitney U test. BMI: body mass index; CI: confidence interval; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; GRIm-Score: Gustave Roussy Immune Score; IQR: interquartile range; ICI: immune-checkpoint inhibitor; LDH: lactate dehydrogenase; NA: not assessed; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; SQ; squamous cell carcinoma; TKI: tyrosine kinase inhibitor; ULN: upper limit of normal.

Backgrounds

Sex (N)

Male/female

35/20

14/7

1.00^a

Age (years)

Median (IQR)

69 (62.5 - 73)

71 (68 - 75)

0.29^b

Smoking status (N)

NS/Ex, CS

12/43

4/17

1.00^a

BMI

Median (IQR)

22.7 (21.0 - 25.1)

22.5 (18.2 - 24.0)

0.26^b

≥ 18.5/< 18.5 (N)

48/7

14/7

0.051^a

Histology (N)

Non-SQ/SQ

42/13

16/5

1.00^a

EGFR mutation (N)

(-) or NA/(+)

46/9

19/2

0.72^a

PD-L1 status (N)

≥ 50%/1-49%/< 1% /NA

13/9/5/28

1/5/3/11

0.25^a

ECOG-PS (N)

0-1/2/3

43/11/1

11/6/4

0.02^a

Metastatic sites (N)

< 3/≥ 3

25/30

10/11

1.00^a

Treatment

ICI regimen (N)

Nivolumab

Pembrolizumab

Atezolizumab

0.08^a

Previous treatment (N)

Anti-angiogenic drug

0.62^a

EGFR-TKIs

0.21^a

Radiotherapy

0.77^a

Further line treatment (N)

0.32^a

ICI efficacy

ORR (%) (95% CI)

18.2 (9.1 - 30.9)

4.8 (0.1 - 23.8)

0.27^a

DCR (%) (95% CI)

41.8 (28.7 - 55.9)

19.0 (5.4 - 41.9)

0.11^a

Laboratory data

NLR

Median (IQR)

2.64 (1.89 - 3.89)

5.85 (3.57 - 7.18)

< 0.01^b

> 6 (N)

< 0.01^a

LDH (U/L)

Median (IQR)

208 (184.5 - 242.5)

324 (228 - 387)

< 0.01^b

> ULN (N)

< 0.01^a

Albumin (g/dL)

Median (IQR)

3.8 (3.5 - 4.0)

3.1 (2.8 - 3.2)

< 0.01^b

< 3.5 g/dL (N)

< 0.01^a

**Table 2.** Baseline Characteristics, Treatment, and Laboratory Data According to RMH score (N = 76)
N	RMH score	P
^aFisher’s exact test, ^bMann-Whitney U test. BMI: body mass index; CI: confidence interval; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; IQR: interquartile range; ICI: immune-checkpoint inhibitor; LDH: lactate dehydrogenase; NA: not assessed; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; RMH score: Royal Marsden Hospital prognostic score; SQ; squamous cell carcinoma; TKI: tyrosine kinase inhibitor; ULN: upper limit of normal.
Backgrounds
Sex (N)
Male/female	31/13	18/14	0.23^a
Age (years)
Median (IQR)	69.5 (63 - 73)	70.5 (61.25 - 75)	0.63^b
Smoking status (N)
NS/Ex, CS	7/37	9/23	0.26^a
BMI
Median (IQR)	22.0 (20.5 - 23.8)	23.1 (19.3 - 26.5)	0.20^b
≥ 18.5/< 18.5 (N)	36/8	26/6	1.00^a
Histology (N)
Non-SQ/SQ	30/14	28/4	0.06^a
EGFR mutation (N)
(-) or NA/(+)	35/9	30/2	0.11^a
PD-L1 status (N)
≥ 50%/1-49%/< 1%/NA	9/10/3/22	5/5/5/17	0.57^a
ECOG-PS (N)
0-1/2/3	33/9/2	21/8/3	0.58^a
Metastatic sites (N)
< 3/≥ 3	28/16	7/25	< 0.01^a
Treatment
ICI regimen (N)			0.77^a
Nivolumab	32	26
Pembrolizumab	9	4
Atezolizumab	3	2
Previous treatment (N)
Anti-angiogenic drug	18	18	0.25^a
EGFR-TKIs	11	4	0.25^a
Radiotherapy	11	8	1.00^a
Further line treatment (N)	24	16	0.82^a
ICI efficacy
ORR (%) (95% CI)	20.5 (9.8 - 35.3)	6.2 (0.8 - 20.8)	0.11^a
DCR (%) (95% CI)	40.9 (26.3 - 56.8)	25.0 (11.5 - 43.4)	0.15^a
Laboratory data
NLR
Median (IQR)	2.92 (2.02 - 3.99)	3.75 (2.30 - 5.47)	0.14^b
> 6 (N)	4	7	0.19^a
LDH (U/L)
Median (IQR)	197 (179 - 219)	304 (233.8 - 344)	< 0.01^b
> ULN (N)	9	26	< 0.01^a
Albumin (g/dL)
Median (IQR)	3.8 (3.5 - 4.0)	3.2 (2.9 - 3.6)	< 0.01^b
< 3.5 g/dL (N)	8	22	< 0.01^a

Table 2. Baseline Characteristics, Treatment, and Laboratory Data According to RMH score (N = 76)

RMH score

Low (N = 44)

High (N = 32)

^aFisher’s exact test, ^bMann-Whitney U test. BMI: body mass index; CI: confidence interval; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; IQR: interquartile range; ICI: immune-checkpoint inhibitor; LDH: lactate dehydrogenase; NA: not assessed; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; RMH score: Royal Marsden Hospital prognostic score; SQ; squamous cell carcinoma; TKI: tyrosine kinase inhibitor; ULN: upper limit of normal.

Backgrounds

Sex (N)

Male/female

31/13

18/14

0.23^a

Age (years)

Median (IQR)

69.5 (63 - 73)

70.5 (61.25 - 75)

0.63^b

Smoking status (N)

NS/Ex, CS

7/37

9/23

0.26^a

BMI

Median (IQR)

22.0 (20.5 - 23.8)

23.1 (19.3 - 26.5)

0.20^b

≥ 18.5/< 18.5 (N)

36/8

26/6

1.00^a

Histology (N)

Non-SQ/SQ

30/14

28/4

0.06^a

EGFR mutation (N)

(-) or NA/(+)

35/9

30/2

0.11^a

PD-L1 status (N)

≥ 50%/1-49%/< 1%/NA

9/10/3/22

5/5/5/17

0.57^a

ECOG-PS (N)

0-1/2/3

33/9/2

21/8/3

0.58^a

Metastatic sites (N)

< 3/≥ 3

28/16

7/25

< 0.01^a

Treatment

ICI regimen (N)

0.77^a

Nivolumab

Pembrolizumab

Atezolizumab

Previous treatment (N)

Anti-angiogenic drug

0.25^a

EGFR-TKIs

0.25^a

Radiotherapy

1.00^a

Further line treatment (N)

0.82^a

ICI efficacy

ORR (%) (95% CI)

20.5 (9.8 - 35.3)

6.2 (0.8 - 20.8)

0.11^a

DCR (%) (95% CI)

40.9 (26.3 - 56.8)

25.0 (11.5 - 43.4)

0.15^a

Laboratory data

NLR

Median (IQR)

2.92 (2.02 - 3.99)

3.75 (2.30 - 5.47)

0.14^b

> 6 (N)

0.19^a

LDH (U/L)

Median (IQR)

197 (179 - 219)

304 (233.8 - 344)

< 0.01^b

> ULN (N)

< 0.01^a

Albumin (g/dL)

Median (IQR)

3.8 (3.5 - 4.0)

3.2 (2.9 - 3.6)

< 0.01^b

< 3.5 g/dL (N)

< 0.01^a

Table 3. Multivariate Cox Hazard Proportional Analyses of Overall Survival of All Patients (N = 76)

Variable

GRIm-Score

RMH score

HR (95% CI)

CI: confidence interval; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; GRIm-Score: Gustave Roussy Immune Score; HR: hazard ratio; NLR: neutrophil-to-lymphocyte ratio; RMH score: Royal Marsden Hospital prognostic score; SQ: squamous cell carcinoma. *P < 0.05, **P < 0.01.

Age (years)

< 70

1 (reference)

≥ 70

0.87 (0.48 - 1.59)

0.66

1.13 (0.61 - 2.10)

0.71

Histology

Non-SQ

1 (reference)

0.62 (0.28 - 1.36)

0.23

0.77 (0.35 - 1.71)

0.53

ECOG-PS

0 or 1

1 (reference)

≥ 2

1.80 (0.98 - 3.30)

0.056

1.93 (1.04 - 3.59)

0.04*

No. of metastases

< 3

1 (reference)

≥ 3

1.05 (0.57 - 1.94)

0.88

GRIm-Score

Low (0 - 1)

1 (reference)

High (2 - 3)

3.93 (2.04 - 7.58)

< 0.01**

NLR

< 6

1 (reference)

≥ 6

1.92 (0.85 - 4.34)

0.12

RMH score

Low (0 - 1)

1 (reference)

High (2 - 3)

1.42 (0.78 - 2.57)

0.25

**Table 4.** Multivariate Cox Hazard Proportional Analyses of Progression-Free Survival of All Patients (N = 76)
Variable	GRIm-Score	RMH score
CI: confidence interval; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; GRIm-Score: Gustave Roussy Immune Score; HR: hazard ratio; NA: not assessed; NLR: neutrophil-to-lymphocyte ratio; RMH score: Royal Marsden Hospital prognostic score; SQ: squamous cell carcinoma. P < 0.05, *P < 0.01.
Age (years)
< 70	1 (reference)		1 (reference)
≥ 70	0.60 (0.34 - 1.06)	0.08	0.67 (0.38 - 1.19)	0.17
Histology
Non-SQ	1 (reference)		1 (reference)
SQ	0.92 (0.47 - 1.81)	0.81	0.87 (0.45 - 1.69)	0.68
PD-L1 expression
< 1% or NA	1 (reference)		1 (reference)
≥ 1%	0.57 (0.33 - 0.97)	0.04*	0.67 (0.39 - 1.16)	0.15
ECOG-PS
0 or 1	1 (reference)		1 (reference)
≥ 2	2.32 (1.28 - 4.20)	< 0.01**	2.45 (1.35 - 4.41)	< 0.01**
No. of metastases
< 3	1 (reference)
≥ 3	1.92 (1.10 - 3.33)	0.02*
GRIm-Score
Low (0 - 1)	1 (reference)
High (2 - 3)	1.36 (0.75 - 2.44)	0.31
NLR
< 6			1 (reference)
≥ 6			0.90 (0.42 - 1.90)	0.78
RMH score
Low (0 - 1)			1 (reference)
High (2 - 3)			1.76 (1.03 - 3.02)	0.04*

Table 4. Multivariate Cox Hazard Proportional Analyses of Progression-Free Survival of All Patients (N = 76)

Variable

GRIm-Score

RMH score

HR (95% CI)

CI: confidence interval; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; GRIm-Score: Gustave Roussy Immune Score; HR: hazard ratio; NA: not assessed; NLR: neutrophil-to-lymphocyte ratio; RMH score: Royal Marsden Hospital prognostic score; SQ: squamous cell carcinoma. *P < 0.05, **P < 0.01.

Age (years)

< 70

1 (reference)

≥ 70

0.60 (0.34 - 1.06)

0.08

0.67 (0.38 - 1.19)

0.17

Histology

Non-SQ

1 (reference)

0.92 (0.47 - 1.81)

0.81

0.87 (0.45 - 1.69)

0.68

PD-L1 expression

< 1% or NA

1 (reference)

≥ 1%

0.57 (0.33 - 0.97)

0.04*

0.67 (0.39 - 1.16)

0.15

ECOG-PS

0 or 1

1 (reference)

≥ 2

2.32 (1.28 - 4.20)

< 0.01**

2.45 (1.35 - 4.41)

< 0.01**

No. of metastases

< 3

1 (reference)

≥ 3

1.92 (1.10 - 3.33)

0.02*

GRIm-Score

Low (0 - 1)

1 (reference)

High (2 - 3)

1.36 (0.75 - 2.44)

0.31

NLR

< 6

1 (reference)

≥ 6

0.90 (0.42 - 1.90)

0.78

RMH score

Low (0 - 1)

1 (reference)

High (2 - 3)

1.76 (1.03 - 3.02)

0.04*