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 https://www.wjon.org

Original Article

Volume 15, Number 2, April 2024, pages 223-238

Predictors of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer: Lung Immune Prognostic Index and Immune-Related Toxicity

Figure 1. Disease response rate according to appearance of irAEs for patients with first- and second-line treatment. irAEs: immune-related adverse events.

Figure 2. Disease response rate according to histology and appearance of irAEs. irAEs: immune-related adverse events.

Figure 3. Frequency of appearance of irAEs according to disease reassessment. irAEs: immune-related adverse events.

Figure 4. PFS (a) and OS (b) according to appearance of irAEs. irAEs: immune-related adverse events; OS: overall survival; PFS: progression-free survival.

Figure 5. Frequency of occurrence of toxicity according to LIPI (a), and LIPI and treatment (b). LIPI: lung immune prognostic index.

Figure 6. Response rate according to LIPI three subgroups (a), and two subgroups (b). LIPI: lung immune prognostic index.

Figure 7. Response rate according to ICI and LIPI three subgroups (a), and two subgroups (b). ICI: immune checkpoint inhibitor; LIPI: lung immune prognostic index.

Figure 9. PFS according to LIPI three subgroups (a), and LIPI two subgroups (b). LIPI: lung immune prognostic index; PFS: progression-free survival.

Figure 10. OS according to LIPI three subgroups (a), and LIPI two subgroups (b). LIPI: lung immune prognostic index; OS: overall survival.

**Table 1.** General Characteristics According to LIPI
	All (N = 168)	Good (N = 82)	Intermediate (N = 73)	Poor (N = 13)	P overall
Means (standard deviation) for continuous variables and number of cases (%) for categorical variables. Comparisons between groups are made using ANOVA (continuous variables) and Chi-square with Yates correction (categorical variables). ANOVA: analysis of variance; CR: complete response; LDH: lactate dehydrogenase; LIPI: lung immune prognostic index; NE: not evaluated; NLR: neutrophil-to-lymphocyte ratio; PD: progressive disease; PR: partial response; SD: stable disease.
Age	64.3 (9.11)	66.0 (8.23)	63.5 (9.59)	58.2 (8.99)	0.009
Sex					0.663
Men	130 (77.4%)	65 (79.3%)	56 (76.7%)	9 (69.2%)
Female	38 (22.6%)	17 (20.7%)	17 (23.3%)	4 (30.8%)
Histology					0.543
Adenocarcinoma	116 (69%)	53 (64.6%)	53 (72.6%)	10 (76.9%)
Squamous	52 (31%)	29 (35.4%)	20 (27.4%)	3 (23.1%)
Drug					0.912
Atezolizumab	41 (24.4%)	21 (25.6%)	18 (24.7%)	2 (15.4%)
Nivolumab	18 (10.7%)	9 (11.0%)	7 (9.59%)	2 (15.4%)
Pembrolizumab	109 (64.9%)	52 (63.4%)	48 (65.8%)	9 (69.2%)
NLR	2.46 (1.95)	1.68 (0.60)	2.68 (1.45)	6.18 (4.27)	< 0.001
LDH	244 (132)	179 (25.8)	294 (163)	359 (143)	< 0.001
Response
CR	15 (8.93%)	10 (12.2%)	4 (5.48%)	1 (7.69%)
PR	5 (29.8%)	30 (36.6%)	17 (23.3%)	3 (23.1%)
SD	39 (23.2%)	22 (26.8%)	15 (20.5%)	2 (15.4%)
PD	45 (26.8%)	12 (14.6%)	28 (38.4%)	5 (38.5%)
NE	19 (11.3%)	8 (9.76%)	9 (12.3%)	2 (15.4%)
Progression	103 (61.3%)	46 (56.1%)	46 (63.0%)	11 (84.6%)	0.135
Death	114 (67.9%)	46 (56.1%)	56 (76.7%)	12 (92.3%)	0.003
Alive	54 (32.1%)	36 (43.9%)	17 (23.2%)	1 (7.7%)

Table 1. General Characteristics According to LIPI

All (N = 168)

Good (N = 82)

Intermediate (N = 73)

Poor (N = 13)

P overall

Means (standard deviation) for continuous variables and number of cases (%) for categorical variables. Comparisons between groups are made using ANOVA (continuous variables) and Chi-square with Yates correction (categorical variables). ANOVA: analysis of variance; CR: complete response; LDH: lactate dehydrogenase; LIPI: lung immune prognostic index; NE: not evaluated; NLR: neutrophil-to-lymphocyte ratio; PD: progressive disease; PR: partial response; SD: stable disease.

Age

64.3 (9.11)

66.0 (8.23)

63.5 (9.59)

58.2 (8.99)

0.009

Sex

0.663

Men

130 (77.4%)

65 (79.3%)

56 (76.7%)

9 (69.2%)

Female

38 (22.6%)

17 (20.7%)

17 (23.3%)

4 (30.8%)

Histology

0.543

Adenocarcinoma

116 (69%)

53 (64.6%)

53 (72.6%)

10 (76.9%)

Squamous

52 (31%)

29 (35.4%)

20 (27.4%)

3 (23.1%)

Drug

0.912

Atezolizumab

41 (24.4%)

21 (25.6%)

18 (24.7%)

2 (15.4%)

Nivolumab

18 (10.7%)

9 (11.0%)

7 (9.59%)

2 (15.4%)

Pembrolizumab

109 (64.9%)

52 (63.4%)

48 (65.8%)

9 (69.2%)

NLR

2.46 (1.95)

1.68 (0.60)

2.68 (1.45)

6.18 (4.27)

< 0.001

LDH

244 (132)

179 (25.8)

294 (163)

359 (143)

< 0.001

Response

15 (8.93%)

10 (12.2%)

4 (5.48%)

1 (7.69%)

5 (29.8%)

30 (36.6%)

17 (23.3%)

3 (23.1%)

39 (23.2%)

22 (26.8%)

15 (20.5%)

2 (15.4%)

45 (26.8%)

12 (14.6%)

28 (38.4%)

5 (38.5%)

19 (11.3%)

8 (9.76%)

9 (12.3%)

2 (15.4%)

Progression

103 (61.3%)

46 (56.1%)

46 (63.0%)

11 (84.6%)

0.135

Death

114 (67.9%)

46 (56.1%)

56 (76.7%)

12 (92.3%)

0.003

Alive

54 (32.1%)

36 (43.9%)

17 (23.2%)

1 (7.7%)

**Table 2.** irAEs and Response Rate According to Histology
Histology	Toxicity	Re-evaluation
CR: complete response; irAEs: immune-related adverse events; NE: not evaluated; PD: progressive disease; PR: partial response; SD: stable disease.
Adenocarcinoma	Yes (77)	13	31	21	8	4
	No (39)	0	3	6	21	9
Squamous	Yes (27)	2	12	9	4	0
	No (25)	0	4	3	12	6

Table 2. irAEs and Response Rate According to Histology

Histology

Toxicity

Re-evaluation

CR: complete response; irAEs: immune-related adverse events; NE: not evaluated; PD: progressive disease; PR: partial response; SD: stable disease.

Adenocarcinoma

Yes (77)

No (39)

Squamous

Yes (27)

No (25)

**Table 3.** Response Rate According to Appearance of irAEs for Patients With First- and Second-Line Treatment
	First-line	Second-line
CR: complete response; irAEs: immune-related adverse events; NE: not evaluated; PD: progressive disease; PR: partial response; SD: stable disease.
Response rate			< 0.001			< 0.001
CR	0 (0.00%)	12 (100%)		0 (0.00%)	3 (100%)
PR	5 (14.3%)	30 (85.7%)		2 (13.3%)	13 (86.7%)
SD	5 (26.3%)	14 (73.7%)		4 (20.0%)	16 (80.0%)
PD	17 (85.0%)	3 (15.0%)		16 (64.0%)	9 (36.0%)
NE	6 (66.7%)	3 (33.3%)		9 (90.0%)	1 (10.0%)

Table 3. Response Rate According to Appearance of irAEs for Patients With First- and Second-Line Treatment

First-line

Second-line

No toxicity (N = 33)

Toxicity (N = 62)

P overall

No toxicity (N = 31)

Toxicity (N = 42)

P overall

CR: complete response; irAEs: immune-related adverse events; NE: not evaluated; PD: progressive disease; PR: partial response; SD: stable disease.

Response rate

< 0.001

0 (0.00%)

12 (100%)

0 (0.00%)

3 (100%)

5 (14.3%)

30 (85.7%)

2 (13.3%)

13 (86.7%)

5 (26.3%)

14 (73.7%)

4 (20.0%)

16 (80.0%)

17 (85.0%)

3 (15.0%)

16 (64.0%)

9 (36.0%)

6 (66.7%)

3 (33.3%)

9 (90.0%)

1 (10.0%)

**Table 4.** irAEs Profile According to LIPI
	All (N = 168)	Good (N = 82)	Intermediate (N = 73)	Poor (N = 13)	P overall
irAEs: immune-related adverse events; LIPI: lung immune prognostic index.
Toxicity	104 (61.9%)	61 (74.4%)	36 (49.3%)	7 (53.8%)	0.004
Dermatological
No	142 (84.5%)	69 (84.1%)	62 (84.9%)	11 (84.6%)	1.000
Yes	26 (15.5%)	13 (15.9)	11 (15.1%)	2 (15.4%)	1.000
Gastrointestinal
No	126 (75.0%)	61 (74.4%)	55 (75.3%)	10 (76.9%)	1.000
Yes	42 (25.0%)	21 (25.6%)	18 (24.7%)	3 (23.1%)	1.000
Lung
No	152 (90.5%)	72 (87.8%)	68 (93.2%)	12 (92.3%)	0.520
Yes	16 (9.5%)	10 (12.2%)	5 (6.85%)	1 (7.7%)	0.520
Endocrine
No	111 (66.1%)	51 (62.2%)	52 (71.2%)	8 (61.5%)	0.457
Yes	57 (33.9%)	31 (37.8%)	21 (28.8%)	5 (38.5%)	0.457
Musculoeskeletal
No	147 (87.5%)	71 (86.6%)	64 (87.7%)	12 (92.3%)	1.000
Yes	21 (12.5%)	11 (13.4%)	9 (12.3%)	1 (7.69%)	1.000
Renal
No	159 (94.6%)	77 (93.9%)	69 (94.5%)	13 (100%)	1.000
Yes	9 (5.4%)	5 (6.1%)	4 (5.5%)	0 (0%)	1.000
Neurological
No	163 (97.0%)	79 (96.3%)	72 (98.6%)	12 (92.3%)	0.267
Yes	5 (3%)	3 (3.7%)	1 (1.4%)	1 (7.7%)	0.267
Hematological
No	161 (96.4%)	75 (92.6%)	73 (100%)	13 (100%)	0.039
Yes	6 (3.6%)	6 (7.4%)	0 (0%)	0 (0%)	0.039
Cardiovascular
No	161 (95.8%)	76 (92.7%)	72 (98.6%)	13 (100%)	0.196
Yes	7 (4.2%)	6 (7.3%)	1 (1.4%)	0 (0%)	0.196
Ophthalmological
No	159 (94.6%)	79 (96.3%)	68 (93.2%)	12 (92.3%)	0.473
Yes	9 (5.4%)	3 (3.7%)	5 (6.8%)	1 (7.3%)	0.473

Table 4. irAEs Profile According to LIPI

All (N = 168)

Good (N = 82)

Intermediate (N = 73)

Poor (N = 13)

P overall

irAEs: immune-related adverse events; LIPI: lung immune prognostic index.

Toxicity

104 (61.9%)

61 (74.4%)

36 (49.3%)

7 (53.8%)

0.004

Dermatological

142 (84.5%)

69 (84.1%)

62 (84.9%)

11 (84.6%)

1.000

Yes

26 (15.5%)

13 (15.9)

11 (15.1%)

2 (15.4%)

1.000

Gastrointestinal

126 (75.0%)

61 (74.4%)

55 (75.3%)

10 (76.9%)

1.000

Yes

42 (25.0%)

21 (25.6%)

18 (24.7%)

3 (23.1%)

1.000

Lung

152 (90.5%)

72 (87.8%)

68 (93.2%)

12 (92.3%)

0.520

Yes

16 (9.5%)

10 (12.2%)

5 (6.85%)

1 (7.7%)

0.520

Endocrine

111 (66.1%)

51 (62.2%)

52 (71.2%)

8 (61.5%)

0.457

Yes

57 (33.9%)

31 (37.8%)

21 (28.8%)

5 (38.5%)

0.457

Musculoeskeletal

147 (87.5%)

71 (86.6%)

64 (87.7%)

12 (92.3%)

1.000

Yes

21 (12.5%)

11 (13.4%)

9 (12.3%)

1 (7.69%)

1.000

Renal

159 (94.6%)

77 (93.9%)

69 (94.5%)

13 (100%)

1.000

Yes

9 (5.4%)

5 (6.1%)

4 (5.5%)

0 (0%)

1.000

Neurological

163 (97.0%)

79 (96.3%)

72 (98.6%)

12 (92.3%)

0.267

Yes

5 (3%)

3 (3.7%)

1 (1.4%)

1 (7.7%)

0.267

Hematological

161 (96.4%)

75 (92.6%)

73 (100%)

13 (100%)

0.039

Yes

6 (3.6%)

6 (7.4%)

0 (0%)

0.039

Cardiovascular

161 (95.8%)

76 (92.7%)

72 (98.6%)

13 (100%)

0.196

Yes

7 (4.2%)

6 (7.3%)

1 (1.4%)

0 (0%)

0.196

Ophthalmological

159 (94.6%)

79 (96.3%)

68 (93.2%)

12 (92.3%)

0.473

Yes

9 (5.4%)

3 (3.7%)

5 (6.8%)

1 (7.3%)

0.473