Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study

Figures & data

Figure 1. Study flow-chart. NSCLC: non-small cell lung cancer; eCRFs: electronic case report form; RECIST: Response evaluation criteria in solid tumors; OS: overall survival; PFS: progression-free survival; 2L: second-line, 3L/LL: third-line or later-line.

Table 1. Demographic and clinical characteristics of patients.

Demographic characteristics	N
Age, year, Mean ± SD	244	60 ± 10
Sex, n (%)	244
Female		48 (19.7)
Male		196 (80.3)
Smoking status, n (%)	79
Nonsmoker		19 (24.1)
Quitted		35 (44.3)
Current smoker		25 (31.6)
Alcohol consumption, n (%)	63
Never consumed		48 (76.2)
Quitted		10 (15.9)
Current consumer		5 (7.9)
Tumor stage, n (%)	221
I-IIIB		38 (17.2)
IV		183 (82.8)
ECOG score, n (%)	241
0		76 (31.5)
1		128 (53.1)
2		34 (14.1)
3		3 (1.2)
Histological type, n (%)	216
Squamous		10 (4.6)
Adenocarcinoma		183 (84.7)
Adenosquamous		14 (6.5)
Unclassified		9 (4.2)
Site of metastasis, n (%)	219
Lungs		105 (47.9)
Liver		31 (14.2)
Brain		36 (16.4)
Lymph node		50 (22.8)
Bones		92 (42.0)
Other		57 (26.0)

2L: second-line, 3L: third-line, LL: later-line, SD: standard deviation, ECOG PS: Eastern Cooperative Oncology Group Performance Status.

Table 2. Treatment-related information of the whole study population (N = 244).

Treatment used prior to nivolumab therapy	n (%)
Carboplatin + Paclitaxel	25 (10.2)
Pemetrexed + Carboplatin	18 (7.4)
Gemcitabine + Cisplatin	10 (4.1)
Paclitaxel + Cisplatin	9 (3.7)
Cisplatin + Pemetrexed	6 (2.5)
Docetaxel + Cisplatin	3 (1.2)
Carboplatin + Paclitaxel + Radiotherapy	2 (0.8)
Carboplatin + Pembrolizumab	2 (0.8)
Gemcitabine + Carboplatin	2 (0.8)
Carboplatin + NabPaclitaxel	1 (0.4)
Carboplatin + Pemetrexed + Radiotherapy	1 (0.4)
Carboplatin + Radiotherapy	1 (0.4)
Cisplatin + Etoposide	1 (0.4)
Cisplatin + Etoposide + Radiotherapy	1 (0.4)
Cisplatin + Paclitaxel + Radiotherapy	1 (0.4)
Pemetrexed	1 (0.4)
Unknown	160 (65.6)
Nivolumab treatment line, n (%)
Second-line therapy	129 (52.9)
Third- or later-line therapy	115 (47.1)

Table 3. Comparison of demographic and clinical characteristics of the patients in the treatment line groups.

Characteristics	Group 2L	Group 3L/LL	p
Age, year, Mean ± SD	61 ± 10	59 ± 10	0.181*
Median (minimum-maximum)	61 (31-86)	60 (34-79)
Sex, n (%)
Female	23 (17.8)	25 (21.7)	0.443**
Male	106 (82.2)	90 (78.3)
Smoking status, n (%)
Nonsmoker	12 (22.2)	7 (28.0)	0.822**
Quitted	25 (46.3)	10 (40.0)
Current smoker	17 (31.5)	8 (32.0)
Alcohol consumption, n (%)
Never consumed	34 (75.6)	14 (77.8)	1.000***
Quitted	7 (15.6)	3 (16.7)
Current consumer	4 (8.9)	1 (5.6)
Tumor stage, n (%)
Stage I-IIIB	21 (17.8)	17 (16.5)	0.800**
Stage IV	97 (82.2)	86 (83.5)
ECOG score, n (%)
0	38 (29.5)	38 (33.9)	0.263***
1	67 (51.9)	61 (54.5)
2	21 (16.3)	13 (11.6)
3	3 (2.3)	0 (0)
Histologic type, n (%)
Squamous	3 (2.7)	7 (6.8)	0.076***
Adenocarcinoma	95 (84.1)	88 (85.4)
Adenosquamous	7 (6.2)	7 (6.8)
Unclassified	8 (7.1)	1 (1.0)
Site of metastasis, n (%)
Lungs	56 (45.9)	49 (50.5)	0.497**
Liver	19 (15.6)	12 (12.4)	0.499**
Brain	18 (14.8)	18 (18.6)	0.451**
Lymph node	38 (31.1)	12 (12.4)	0.001**
Bones	50 (41)	42 (43.3)	0.730**
Other	34 (27.9)	23 (23.7)	0.486**

*Mann-Whitney U test.

**Chi-square test. Bold value is significant at p < 0.05.

***Fisher’s exact test.

2L: second-line, 3L/LL: third-line or later-line, SD: standard deviation, ECOG PS: Eastern Cooperative Oncology Group Performance Status.

Table 4. Comparison of molecular characteristics (driver mutations) of the patients in the treatment line groups.

Driver mutations	All patients	Group 2L	Group 3L/LL	p
EGFR	12 (14.5)	6 (10.5)	6 (23.1)	0.179**
ALK	12 (14.3)	6 (10.3)	6 (23.1)	0.176**
ROS-1	10 (12.0)	6 (10.5)	4 (15.4)	0.717**
BRAF	9 (11.1)	4 (7.1)	5 (20.0)	0.126**
KRAS	5 (6.2)	2 (3.6)	3 (12.0)	0.168**
PD-L1	37 (44.0)	26 (44.8)	11 (42.3)	0.830*

*Chi-square test.

**Fisher’s exact test.

2L: second-line treatment, 3L/LL: third-line or later-line treatment.

Figure 2. (a) Overall survival and (b) Progression-free survival curve for the whole study population.

Table 5. Treatment response rates by RECIST criteria according to the treatment line groups.

	All patients N = 189	Group 2L N = 101	Group 3L/LL N = 88
	n (%)	n (%)	n (%)
Complete response (CR)	7 (3.7)	4 (4.0)	3 (3.4)	0.264*
Partial response (PR)	52 (27.5)	31 (30.7)	21 (23.9)
Stable disease (SD)	26 (13.8)	17 (16.8)	9 (10.2)
Progressive disease (PD)	104 (55.0)	49 (48.5)	55 (62.5)
Objective response rate (ORR)	59 (31.2)	35 (34.7)	24 (27.3)	0.275**

*Fisher’s exact test.

**Chi-square.

RECIST: Response evaluation criteria in solid tumors, 2L: second-line, 3L/LL: third-line or later-line.

Table 6. Frequency of adverse events according to the treatment line groups.

	All patients		Group 2L		Group 3L/LL
Adverse Events	N	n (%)	N	n (%)	N	n (%)	p
Presence of at least 1 adverse event	244	95 (38.9)	129	45 (34.9)	115	50 (43.5)	0.169*
Fatigue	238	39 (16.4)	127	19 (15.0)	111	20 (18.0)	0.525*
Toxicity	240	35 (14.6)	129	16 (12.4)	111	19 (17.1)	0.302*
Poor appetite	238	28 (11.8)	128	13 (10.2)	110	15 (13.6)	0.406*
Anemia	241	28 (11.6)	127	12 (9.4)	114	16 (14.0)	0.267*
Elevated creatinine	238	13 (5.5)	126	5 (4)	112	8 (7.1)	0.282*
Hypothyroidism	224	12 (5.4)	119	7 (5.9)	105	5 (4.8)	0.710*
Lymphopenia	238	12 (5.0)	126	7 (5.6)	112	5 (4.5)	0.701*
Pneumonitis	237	9 (3.8)	125	5 (4.0)	112	4 (3.6)	1.000**
Nausea	238	8 (3.4)	127	3 (2.4)	111	5 (4.5)	0.478**
Elevated ALT/AST	237	7 (3.0)	125	3 (2.4)	112	4 (3.6)	0.710**
Pruritus	239	7 (2.9)	128	2 (1.6)	111	5 (4.5)	0.255**
Rash/skin toxicity	230	6 (2.6)	123	0 (0.0)	107	6 (5.6)	0.009**
Neutropenia	239	5 (2.1)	126	4 (3.2)	113	1 (0.9)	0.373**
Elevated amylase	189	4 (2.1)	109	2 (1.8)	80	2 (2.5)	–
Elevated lipase	187	4 (2.1)	108	3 (2.8)	79	1 (1.3)	–
Diarrhea/Colitis	238	4 (1.7)	127	3 (2.4)	111	1 (0.9)	–
Hypercalcemia	240	4 (1.7)	126	2 (1.6)	114	2 (1.8)	–
Arthralgia	244	3 (1.2)	129	3 (2.3)	115	0 (0.0)	–
Hypophosphatemia	187	2 (1.1)	107	1 (0.9)	80	1 (1.3)	–
Fever	237	2 (0.8)	126	1 (0.8)	111	1 (0.9)	–
Hypocalcemia	237	2 (0.8)	126	1 (0.8)	111	1 (0.9)	–
Hypophysitis	244	2 (0.8)	129	1 (0.8)	115	1 (0.9)	–
Hyperthyroidism	244	2 (0.8)	129	2 (1.6)	115	0 (0.0)	–
Thyroiditis	244	2 (0.8)	129	2 (1.6)	115	0 (0.0)	–
Neuropathic pain	244	2 (0.8)	129	0 (0.0)	115	2 (1.7)	–
Adrenal insufficiency	244	2 (0.8)	129	1 (0.8)	115	1 (0.9)	–
Elevated CPK	189	1 (0.5)	109	1 (0.9)	80	0 (0.0)	–
Abdominal pain	244	1 (0.4)	129	0 (0.0)	115	1 (0.9)	–
Pancreatitis	237	1 (0.4)	126	1 (0.8)	111	0 (0.0)	–
Stomatitis/dry mouth	239	1 (0.4)	127	0 (0.0)	112	1 (0.9)	–
Infusion-induced hypersensitivity reaction	228	1 (0.4)	125	0 (0.0)	103	1 (1)	–
Thrombocytopenia	238	1 (0.4)	125	0 (0.0)	113	1 (0.9)	–
Deep vein thrombosis	244	1 (0.4)	129	1 (0.8)	115	0 (0.0)	–

*Chi-square test.

**Fisher’s exact test. Bold value is significant at p < 0.05.

2L: second-line, 3L/LL: third-line or later-line, ALT/AST: alanine transaminase/aspartate aminotransferase CPK: creatine phosphokinase.

Table 7. Reasons for discontinuation of nivolumab therapy.

	All patients N = 114	Group 2L N = 61	Group 3L/LL N = 53	p
Reasons	n (%)	n (%)	n (%)
Disease progression	70 (61.4)	35 (57.4)	35 (66.0)	0.343*
No response	17 (14.9)	11 (18)	6 (11.3)	0.316*
Toxicity	4 (3.5)	1 (1.6)	3 (5.7)	-**
Patient’s decision	1 (0.9)	0 (0)	1 (1.9)	-**
Other	22 (19.3)	14 (23)	8 (15.1)	0.289*

*Chi-square test.

**Could not analyzed due to insufficient sample size.

2L: second-line, 3L/LL: third-line or later-line.