Intrapulmonic Cavity or Necrosis on Baseline CT Scan Serves as an Efficacy Predictor of Anti-PD-(L)1 Inhibitor in Advanced Lung Squamous Cell Carcinoma

Figures & data

Table 1 Patient Characteristics

		Total	Cavity and/or Necrosis N (%)		p-value
			Positive	Negative
		N (%)	N (%)	N (%)
Gender	Male	89 (95.7%)	41 (93.2%)	48 (98.0%)	0.534
	Female	4 (4.3%)	3 (6.8%)	1 (2.0%)
Smoking	Light or never	7 (7.5%)	3 (6.8%)	4 (8.2%)	0.806
	Heavy	86 (92.5%)	41 (93.2%)	45 (91.8%)
Age	$\overline{\text{X}}$±SD	61.3±8.8	60.8±9.1	61.8±8.7	0.565
ECOG PS	0	1 (1.1%)	1 (2.3%)	0 (0.0%)	0.567
	1	90 (96.8%)	42 (95.5%)	48 (98.0%)
	2	2 (2.2%)	1 (2.3%)	1 (2.0%)
Sum of tumor lesion diameters	$\overline{\text{X}}$±SD	67.7±38.8	47.5±23.1	85.7±41.1	<0.001*
Brain metastases	Presence	10 (10.8%)	3 (6.8%)	7 (14.3%)	0.205
	Absence
Liver metastases	Presence	13 (14.0%)	8 (18.2%)	5 (10.2%)	0.405
	Absence
Bone metastases	Presence	25 (26.9%)	6 (13.6%)	19 (38.8%)	0.009*
	Absence
LDH	$\overline{\text{X}}$±SD	244.1±136.0	212.8±54.9	272.2±176.2	0.035*
	≤ 250 IU/L	70 (75.3%)	35 (79.5%)	35 (71.4%)	0.506
	>250 IU/L	23 (24.7%)	9 (20.5%)	14 (28.6%)
NLR	$\overline{\text{X}}$±SD	3.5 (2)	3.3 (1.9)	3.8 (2.0)	0.272
	≤ 3.0	44 (47.3%)	25 (56.8%)	19 (38.8%)	0.125
	>3.0	49 (52.7%)	19 (43.2%)	30 (61.2%)
PD-L1 TPS	Done
	0(0%)	9 (28.1%)	3 (27.3%)	6 (28.6%)	0.345
	1(1–49%)	15 (46.9%)	5 (45.5%)	10 (47.6%)
	2(>50%)	8 (25.0%)	3 (27.3%)	5 (23.8%)
	Not done	61 (65.6%)	33 (75.0%)	28 (57.1%)
Treatment model	Monotherapy	39 (41.9%)	19 (43.2%)	20 (40.8%)	0.983
	Combination therapy	54 (58.1%)	25 (56.8%)	29 (59.2%)
Treatment line	1st	43 (46.2%)	17 (38.6%)	26 (53.1%)	0.102
	2nd	36 (38.7%)	22 (50.0%)	14 (28.6%)
	≥3rd	14 (15.1%)	5 (11.4%)	9 (18.4%)
ICI agent	Nivolumab	11 (11.80%)	4 (9.10%)	7 (14.30%)	0.607
	Pembrolizumab	15 (16.10%)	9 (20.50%)	6 (12.20%)
	Camrelizumab	19 (20.40%)	10 (22.70%)	9 (18.40%)
	Sintilimab	24 (25.80%)	9 (20.50%)	15 (30.60%)
	Others	24 (25.80%)	12 (27.30%)	12 (24.50%)

Notes: Others: Atezolizumab, Avelumab, Tislelizumab, Sugemalimab, Toripalimab ang HLX10. *Indicates statistically significant p-values.

Abbreviations: PS, performance status; ICI, immune checkpoint inhibitor; CRP, C-reactive protein; LDH, lactate dehydrogenase; NLR, neutrophil-to-lymphocyte ratio.

Table 2 Summary of Response in Study Population, ICI Monotherapy Subgroup and ICI Combination Therapy Group

		Total N=93	Cavity and/or Necrosis		p-value
			Positive N=44	Negative N=49
Objective response
Monotherapy	N=39	9 (23.1%)	2 (10.0%)	7 (36.8%)	0.047*
Combination therapy	N=54	30 (55.6%)	13 (44.8%)	17 (68.0%)	0.088
Total	N=93	39 (41.9%)	15 (30.6%)	24 (54.5%)	0.020*

Note: *Indicates statistically significant p-values.

Table 3 Univariable and Multivariable Analyses of Objective Response Rate

	Univariable Model		Multivariable Model
	OR (95% CI)	p-value	OR (95% CI)	p-value
Sum of tumor lesion diameters > 67.7 cm^†	0.742 (0.322–1.710)	0.484
LDH >250 IU/L	1.925 (0.705–5.258)	0.202
NLR >3	1.316 (0.576–3.006)	0.515
Cavity and/or necrosis	2.720 (1.163–6.359)	0.021*	4.042 (1.149–10.908)	0.006*
PD-L1 TPS ≥1%	0.536 (0.089–3.210)	0.494
PD-L1 TPS ≥50%	0.686 (0.128–3.683)	0.661
Treatment line
≥3^rd (reference)		0.046*
1^st	0.339 (0.145–0.796)	0.013
2^nd	1.576 (0.996–2.494)	0.052
Combination therapy	0.240 (0.096–0.601)	0.002*	0.285 (0.102–0.799)	0.017*

Notes: ^†67.7 cm represented the mean of the sum of tumor lesion diameters in all LSCC patients. *Indicates statistically significant p-values.

Abbreviations: CI, confidence interval; OR, odd ratio.

Table 4 Univariable and Multivariable Analyses of Progression Free Survival

	Univariable Model		Multivariable Model
	HR (95% CI)	p-value	HR (95% CI)	p-value
Brain metastases	1.855 (1.117–3.078)	0.017*	2.531 (1.471–4.356)	<0.001*
Liver metastases	1.466 (0.926–2.319)	0.103
Bone metastases	1.256 (0.870–1.813)	0.224
LDH >250 IU/L	1.473 (1.011–2.145)	0.044*	1.436 (0.977–2.112)	0.066
NLR >3	1.169 (0.842–1.624)	0.350
PD-L1 TPS ≥1%	1.086 (0.618–1.911)	0.774
PD-L1 TPS ≥50%	1.126 (0.590–2.150)	0.720
Cavity and/or necrosis	1.644 (1.180–2.346)	0.004*	1.729 (1.203–2.484)	0.003*
Combination therapy	0.517 (0.372–0.719)	<0.001*	0.417 (0.292–0.595)	<0.001*
Sum of tumor lesion diameters > 67.7 cm*	1.091 (0.781–1.517)	0.605

Note: *Indicates statistically significant p-values.

Abbreviations: CI, confidence interval; HR, hazard ratio.

Figure 1 Progression free survival of advanced LSCC patients with versus without intrapulmonic necrosis or cavity on baseline CT scan. (A) PFS in the study population. (B) PFS in the ICI monotherapy subgroup. (C) PFS in the ICI combination subgroup.