Use of programmed cell death protein ligand 1 assay to predict the outcomes of non-small cell lung cancer patients treated with immune checkpoint inhibitors

Table 1 Correlation between nivolumab activity and outcome and programmed cell death protein ligand 1 immunohistochemestry score

Author/study	Marker antibody	Tumor type	Treatment line	PD-L1 cutoff	N pts	Response (%)	mPFS mo (95%CI)	mOS mo (95%CI)
Nivolumab
Gettinger et al[8] Phase I	Dako 28-8	NSCLC	> 2	≥ 5 %	33	15	3.3 (1.8-7.5)	7.8 (5.6-21.7)
				< 5%	35	14	1.8 (1.7-2.3)	10.5 (5.2-14.8)
Rizvi et al[9] CM 063 Phase II	Dako 28-8	Squamous	≥ 2	≥ 5%	25	24	NR	NR
		NSCLC		< 5%	51	14	NR	NR
Brahmer et al[10] CM 017 Phase III	Dako 28-8	Squamous	> 1	≥ 10%	36	19	3.7 (NR)	11 (NR)
		NSCLC		< 10%	81	16	2.3 (NR)	8.2 (NR)
				≥ 5%	42	21	4.8 (NR)	10 (NR)
				< 5%	75	15	2.2 (NR)	8.5 (NR)
				≥ 1%	63	17	3.3 (NR)	9.3 (NR)
				< 1%	54	17	3.1 (NR)	8.7 (NR)
Borgheai et al[11] CM 057 Phase III	Dako 28-8	Non squamous	> 1	≥ 10%	86	37	5.0 (NR)	19.9 (NR)
		NSCLC		< 10%	145	11	2.1 (NR)	9.9 (NR)
				≥ 5%	95	34	5.0 (NR)	19.4 (NR)
				< 5%	136	14	2.1 (NR)	9.8 (NR)
				≥ 1%	123	31	4.2 (NR)	17.7 (NR)
				< 1%	108	9	2.1 (NR)	10.5 (NR)
Gettinger et al[12] CM 012 Phase I	Dako 28-8	NSCLC	1	≥ 50%	12	50	NR	NR
				< 50%	34	15	NR	NR
				≥ 25%	18	44	NR	NR
				< 25%	28	11	NR	NR
				≥ 10%	20	40	NR	NR
				< 10%	26	12	NR	NR
				≥ 5%	26	31	NR	NR
				< 5%	20	15	NR	NR
				≥ 1%	32	28	NR	NR
				< 1%	14	14	NR	NR
Rizvi et al[13] CM012 Phase I	Dako 28-8	NSCLC	1	≥ 1%	23	48	6.0 (< 0.1+-21.8)	20.2 (6.2-28.8+)
				< 1%	21	43	5.2 (0.9+-28.7+)	19.2 (4.5-29.7+)
Socinski et al[14] CM 026 Phase III	Dako 28-8	NSCLC	1	≥ 5%	NR	76.80	NR	NR
				< 5%	NR	NR	NR	NR
				≥ 25%	NR	48.70	NR	NR
				< 25%	NR	NR	NR	NR
				≥ 50%	NR	32.50	NR	NR
				< 50%	NR	NR	NR	NR
				≥ 75%	NR	20.70	NR	NR
				< 75%	NR	NR	NR	NR

CM: CheckMate; NR: Not reported; pts: Patients; NSCLC: Non-small cell lung cancer; PD-L1: Programmed cell death protein ligand 1; mPFS: Median progression free survival; mOS: Median overall survival.

Table 2 Correlation between pembrolizumab activity and outcome and programmed cell death protein ligand 1 immunohistochemestry score

Author/study	Marker antibody	Tumor type	Treatment line	PD-L1 cutoff	N pts	Response	mPFSmo (95%CI)	mOSmo (95%CI)
Pembrolizumab
Garon et al[15] KN001	Dako 22C3	NSCLC	≥ 1	≥ 50%	73	45.20%	6.4 (4.2-NR)	NR (NR-NR)
				1%-49%	103	17%	4.1 (2.3-4.4)	10.6 (7.3-NR)
				< 1%	28	3%	4 (2.1-6.2)	10.4 (5.8-NR)
Herbst et al[16] KN010	Dako 22C3	NSCLC	≥ 2	≥ 50%	290	30%	14.9 (10.4-NR)	5.0 (4.0-6.9)
				1%-49%	400	10%	17.3 (11.8-NR)	5.2 (4.1-8.1)
Reck et al[17] KN024 Phase III	Dako 22C3	NSCLC	1	≥ 50%	305	44.80%	10.3 (6.7-NR)	NA
Langer et al[18] KN021 Phase III	Dako 22C3	Non squamous	1	≥ 50%	20	80%	13 (8.3-NR)	NA
		NSCLC		1%-49%	19	29%
				< 1%	21	57%

KN: KeyNote; NR: not reported; pts: Patients; NA: Not available; NSCLC: Non-small cell lung cancer; PD-L1: Programmed cell death protein ligand 1; mPFS: Median progression free survival; mOS: Median overall survival.

Table 3 Correlation between atezolizumab activity and outcome and programmed cell death protein ligand 1 immunohistochemestry score

Author/study	Marker antibody	Tumor type	Treatment line	PD-L1 cutoff	N pts	Response (%)	mPFS mo (95%CI)	mOS mo (95%CI)
Atezolizumab							NR	NR
							NR	NR
							NR	NR
							NR	NR
Herbst et al[19] Phase I	Ventana SP142	NSCLC	≥ 2	Score 3	6	83	7.8 (2.7-12.3)	15.5 (9.8-NA)
				Score 2	7	14	3.4 (1.4-6.9)	15.1 (8.4-NA)
				Score 1	13	15	3.0 (2.8-4.1)	15.5 (11.1-NA)
				Score 0	20	20	4.1 (2.7-5.6)	9.7 (6.7-12.0)
Fehrenbacher et al[20] POPLAR Phase II	Ventana SP142	NSCLC	≥ 2	Score 3	24	37.50	4.2 (2.9-7.0)	20.5 (17.5-NA)
				Score 2	50	22.00	4.1 (2.8-5.3)	16.3 (13.3-20.1)
				Score 1	93	18.30	4.1 (2.9-4.3)	15.7 (12.6-18.0)
				Score 0	51	14.60	4.0 (3.1-4.2)	12.6 (9.6-15.2)
Rittmeyer et al[21] OAK Phase III	Ventana	NSCLC	≥ 2	Score 3	72	30.60	7.3 (4.9-12.0)	26.9 (12.0-NA)
	SP142			Score 2	129	22.50	7.3 (5.7-9.7)	23.5 (18.1-NA)
				Score 1	241	17.80
				Score 0	80	7.80	7.6 (4.0-9.7)	23.5 (18.1-NA)
Wakelee et al[22] and Antonia et al[23] BIRCH Phase II	Ventana	NSCLC	1	Score 3	65	34
	SP142			TC2/3 or IC2/3	138	25
				Score 2	73	18

Score 3: PDL1 expression levels TC3 or IC3 (≥ 50% on TC or ≥ 10% on IC); Score 2: TC2 or IC2 (≥ 5%-< 50% on TC or ≥ 5% -< 10% IC); Score 1: TC1 or IC1 (≥ 1% - < 5% on TC or IC); Score 0: TC0 and IC0 (< 1% on TC and IC). IC: Tumor-infiltrating immune cell; TC: Tumor cell; NR: Not reported; pts: Patients; NA: Not available; NSCLC: Non-small cell lung cancer; PD-L1: Programmed cell death protein ligand 1; mPFS: Median progression free survival; mOS: Median overall survival.

Table 4 Correlation between durvalumab and avelumab activity and outcome and programmed cell death protein ligand 1 immunohistochemestry score

Author/study	Marker antibody	Tumor type	Treatment line	PD-L1 cutoff	N pts	Response (%)	mPFS mo (95%CI)	mOS mo (95%CI)
Durvalumab
Gulley et al[24] Phase 1/2	Ventana SP263	NSCLC	1	≥ 25%	43	25
				< 5%	8	12
Avelumab
Verschraegen etal[25] Phase 1b	?	NSCLC	≥ 2	≥ 1%	118	14.40	11.7 wk	NR
				< 1%	20	10	5.9 wk	NR
Sheng et al[26] Javelin Phase Ib	?	NSCLC	1	≥ 1%	35	20	NR	NR
				< 1%	10	0	NR	NR

NR: Not reported; pts: Patients; NSCLC: Non-small cell lung cancer; PD-L1: Programmed cell death protein ligand 1; mPFS: Median progression free survival; mOS: Median overall survival.