5-Year survival in Danish patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitor monotherapy

Figures & data

Table 1. Baseline characteristics according to ICI administered in 1st and ≥2nd line.

Baseline characteristics	All patients (n = 729)	ICI in 1st line (n = 321)	ICI in ≥2nd line (n = 408)	p-Value
Age
Median (years), range	69 (35-92)	69 (39–92)	68 (35-86)	0.021
≥75, n (%)	164 (22)	83 (26)	81 (20)	0.054
Sex, n (%)				0.042
Female	371 (51)	177 (55)	194 (48)
Male	358 (49)	144 (45)	214 (52)
Smoking history, n (%)				0.102
Never	35 (5)	20 (6)	15 (4)
Current	232 (32)	111 (35)	121 (30)
Former	460 (63)	189 (59)	271 (66)
Missing	2 (0)	1 (0)	1 (0)
Histological subtype, n (%)				0.001
Non-squamous	526 (72)	251 (78)	275 (67)
Squamous	203 (28)	70 (22)	133 (33)
TNM stage				<0.001
III	107 (15)	66 (21)	41 (10)
IV	622 (85)	255 (79)	367 (90)
PD-L1 TPS, n (%)				<0.001
<0%	30 (4)	1 (0)	29 (7)
<50%	160 (22)	11 (3)	149 (37)
≥50%	448 (61)	309 (96)	139 (34)
Missing	91 (12)	0	91 (22)
EGFR mutation, n (%)				0.001
Yes	12 (2)	2 (1)	10 (3)
No	524 (72)	254 (79)	270 (66)
Not assessed	193 (26)	65 (20)	128 (31)
Performance status (PS), n (%)				0.391
0	164 (22)	82 (26)	82 (20)
1	417 (57)	180 (56)	237 (58)
≥2	128 (18)	59 (18)	69 (17)
Missing	20 (3)	0	20 (5)
Charlson’s Comorbidity Index (CCI), n (%)				0.526
0	240 (33)	100 (31)	140 (34)
1	202 (28)	95 (30)	107 (26)
≥2	287 (39)	126 (39)	161 (39)
ICI-drug, n (%)				<0.001
Nivolumab	202 (28)	5 (2)	197 (48)
Pembrolizumab	515(71)	315 (98)	200 (49)
Atezolizumab	12 (2)	1 (0)	11 (3)
Distant metastatic site, n (%)	n = 639	n = 256	n = 383
Brain	91 (12)	28 (9)	63 (15)	0.006
Liver	97 (13)	30 (9)	67 (16)	0.005
Adrenal gland	126 (17)	56 (17)	70 (17)	0.919
Bone	218 (30)	94 (29)	124 (30)	0.746
Other	107 (15)	48 (15)	59 (14)	0.852
Autoimmunity, yes, n (%)	68 (9)	25 (8)	43(11)	0.205
Baseline blood samples, n (%)
Hemoglobin count <100g/L	48 (7)	9 (3)	39 (10)	<0.001
Missing	1 (0)	0	1 (0)
Leucocytes >11 × 10^9/L	176 (24)	96 (30)	80 (20)	0.001
Missing	2 (0)	1 (0)	1 (0)
Platelets ≥350 × 10^9/L	291 (40)	162 (50)	129 (32)
Missing	1 (0)	0	1 (0)	<0.001
Discontinuation of ICI due to*, n (%)
Progression	381 (52)	150 (47)	231 (57)	0.018
irAE	214 (29)	110 (34)	104 (25)	0.032
Declining PS	110 (15)	32 (10)	78 (19)	0.001
2-Year treatment	67 (9)	31 (10)	36 (9)	0.638
Other reasons	89 (12)	33 (10)	56 (14)	0.158
*Multiple answers possible

CCI: Charlson’s Comorbidity Index; EGFR: epidermal growth factor receptor; ICI: immune checkpoint inhibitor; irAE: immune related adverse events; PD-L1: programmed death ligand-1; PS: performance status; TNM: tumor node metastasis; TPS: tumor proportion score.

Figure 1. (A) Overall survival according to line of ICI (≥2nd line ICI compared to 1st line). (B) PFS according to line of ICI administration (≥2nd line compared to 1st line).

Figure 2. (A) Overall survival according to PD-L1 ≥ 50% versus PD-L1 < 50%. (B) Progression free survival according to PD-L1 ≥ 50% versus PD-L1 < 50%.

Table 2. Survival at 2, 3, 4 and 5 years for those with PD-L1 < 50% versus PD-L1 ≥ 50%.

OS rate (%) according to PD-L1 TPS					OS rate (%) according to PD-L1 TPS and line (1st/≥2nd)
	PD-L1 < 50%	95% CI	PD-L1 ≥ 50%	95% CI	PD-L1 < 50% 1st ≥2 line	95% CI 1st ≥2 line	PD-L1 ≥ 50% 1st ≥2 line	95% CI 1st ≥2 line
2 Year	19.7%	(14.3–25.7)	43.7%	(39.0–48.4)	20.8%	(3.5–47.9)	44.9%	(39.2–50.6)
					19.6%	(14.1–25.8)	40.9%	(32.6–49.0)
3 Year	13.7%	(9.2–19.2)	29.0%	(24.5–33.5)	20.8%	(3.5–47.9)	30.1%	(24.8–35.9)
					13.3%	(8.7–18.9)	26.4%	(19.1–34.3)
4 Year	11.0%	(6.9–16.3)	22.7%	(18.5–27.3)	–	–	24.0%	(18.7–29.7)
					11.2%	(6.9–16.6)	20.5%	(13.7–28.2)
5 Year	6.2%	(3.0–13.8)	19.1%	(14.2–24.5)	– 6.3%	– (2.0–14.0)	12.9% 20.5%	(4.3–26.4) (13.7–28.2)
PFS rate (%) according to PD-L1 TPS					PFS rate (%) according to PD-L1 TPS and line (1st/≥2nd)
	PD-L1 < 50%	95% CI	PD-L1 ≥ 50%	95% CI	PD-L1 < 50% 1st ≥2 line	95% CI 1st ≥2 line	PD-L1 ≥ 50% 1st ≥2 line	95% CI 1st ≥2 line
2 Year	9.9%	(6.2–14.7)	24.5%	(20.6–28.7)	–	–	24.7%	(20.0–29.8)
					10.6%	(6.6–15.6)	23.9%	(17.2–31.3)
3 Year	5.2%	(2.6–9.2)	16.2%	(12.7–20.0)	–	–	16.1%	(11.9–20.8)
					5.6%	(2.8–9.8)	16.2%	(10.4–23.1)
4 Year	4.7%	(2.2–8.5)	13.0%	(9.7–16.7)	–	–	12.7%	(8.8–17.4)
					5.0%	(2.4–9.0)	13.4%	(8.0–20.0)
5 Year	–	–	11.0%	(7.5–15.3)	–	–	–	–
					–	–	11.7%	(6.5–18.6)

Table 3. Uni- and multivariate Cox regression analysis of factors associated with overall survival.

Univariate cox regression of factors associated with overall survival			Multivariate cox regression of factors associated with overall survival
Variable	HR	95% CI	HR	95% CI
Age (≥75 years vs. <75 years)	1.37	1.14–1.66	1.39	1.12–1.73
History of autoimmunity (yes vs. no)	0.91	0.69–1.20
Sex (female vs. male)	0.77	0.66–0.91	0.77	0.64–0.93
Histological subtype (non-squamous vs. squamous)	0.82	0.68–0.98	0.94	0.74–1.19
PD-L1 TPS (≥50 vs. <50%)	0.57	0.48–0.69	0.56	0.46–0.68
TNM disease stage (III vs. IV)	0.97	0.13–6.96
Performance status (≥2 vs. ≤1)	1.86	1.51–2.29	1.88	1.49–2.37
Charlson’s Comorbidity Index Score (≥2 vs. ≤1)	1.03	0.87–1.21	0.98	0.81–1.19
Treatment line (> =2 vs. 1)	1.48	1.25–1.75	1.14	0.90–1.44
Hemoglobin <100 g/L	2.32	1.71–3.14	2.06	1.41–2.83
Leucocytes >11 × 10^9/L	1.33	1.09–1.60	1.34	1.08–1.61
Platelets ≥350 x 10^9/L	1.29	1.09–1.53	1.32	1.09–1.61
Brain metastasis	1.22	0.96–1.56	1.37	1.05–1.78
Liver metastasis	1.73	1.38–2.17	1.37	1.06–1.78
Bone metastasis	1.44	1.20–1.71	1.38	1.14–1.68

Figure 3. Overall survival according to performance status.

Figure 4. (A) Overall survival in patients with PS ≥2 according to PD-L1 ≥ 50% compared to PD-L1 < 50%. (B) Progression free survival in patients with PS ≥2 according to PD-L1 < 50% and ≥50%.

Data availability statement

The study data may be available on request from the corresponding author, Birgitte Bjørnhart. However the data are not publicly available due to the General Data Protection Regulation.