Identifying optimal first-line interventions for advanced non-small cell lung carcinoma according to PD-L1 expression: a systematic review and network meta-analysis

Figures & data

Table 1. Study characteristics

Source	Histology	PD-L1 Expression	Treatment Regimen	Median ages (years)	mPFS (months)	mOS (months)	Median Follow-up Time (months)
								KEYNOTE-021^Citation9,Citation19	Non-squamous	All	PC	62.50	13.00	NR	23.90
Chemo	63.20	8.90	NR	23.90
KEYNOTE-024^Citation11,Citation20	Squamous and Non-squamous	≥50%	Pembro	64.50	10.30	30.00	25.20
			Chemo	66.00	6.00	14.20	25.20
KEYNOTE-042^Citation12	Squamous and Non-squamous	≥1%	Pembro	63.00	7.10	20.00	12.80
			Chemo	63.00	6.40	12.20	12.80
KEYNOTE-042 in China^Citation23	Squamous and Non-squamous	≥1%	Pembro	NR	NR	20.00	11.30
			Chemo	NR	NR	13.70	11.30
KEYNOTE-189^Citation10	Non-squamous	All	PC	65.00	8.80	NR	10.50
			Placebo+Chemo	63.50	4.90	11.30	10.50
KEYNOTE-407^Citation13	Squamous	All	PC	65.00	6.40	15.90	7.80
			Placebo+Chemo	65.00	4.80	11.30	7.80
IMpower-130^Citation14	Non-squamous	All	AC	64.00	7.00	18.60	18.50
			Chemo	65.00	5.50	13.90	18.80
IMpower-131^Citation17,Citation21	Squamous	All	AC	65.00	6.30	14.20	25.50
			Chemo	65.00	5.60	13.50	25.50
IMpower-132^Citation18	Non-squamous	All	AC	64.00	7.60	18.10	14.80
			Chemo	63.00	5.20	13.60	14.80
IMpower-150^Citation16,Citation22	Non-squamous	All	ABC	63.00	8.40	19.80	13.50
			AC	63.00	6.90	19.50	19.60
			BC	63.00	6.80	14.90	19.70

Abbreviation: Pembro: pembrolizumab; Chemo: chemotherapy; Placebo+Chemo: placebo plus chemotherapy; PC: pembrolizumab plus chemotherapy; AC: atezolizumab plus chemotherapy; ABC: atezolizumab plus bevacizumab plus chemotherapy; BC: bevacizumab plus chemotherapy. NR: not reported; PFS: progression-free survival; OS: overall survival.

Table 2. Information on primary outcome of the studies included in network meta-analysis

Source	Overall				PD-L1 ≥ 50%				1%≤PD-L1 < 50%				PD-L1 < 1%				HR for PFS (95%CI)				HR for OS (95%CI)				Incidence of AEs (%)
	No. of Patients		No. of Response		No. of Patients		No. of Response		No. of Patients		No. of Response		No. of Patients		No. of Response										Grade 1–5 AEs		Grade 3–5 AEs
	EM	CM	EM	CM	EM	CM	EM	CM	EM	CM	EM	CM	EM	CM	EM	CM	Overall	PD-L1 ≥ 50%	1%≤PD-L1 < 50%	PD-L1 < 1%	Overall	PD-L1 ≥ 50%	1%≤PD-L1 < 50%	PD-L1 < 1%	EM	CM	EM	CM
KEYNOTE-021^Citation9,Citation19	60	63	-	-	20	17	16	6	19	23	5	9	21	23	12	3	0.53(0.33–0.86)	-	-	-	0.56(0.32–0.95)	-	-	-	94.2	95.7	59.5	50.8
KEYNOTE-024^Citation11,Citation20	154	151	-	-	154	151	70	45	-	-	-	-	-	-	-	-	-	0.50(0.37–0.68)	-	-	-	0.65(0.50–0.86)	-	-	76.6	90	31.2	53.3
KEYNOTE-042^Citation12	637	637	-	-	299	300	118	96	-	-	-	-	-	-	-	-	-	0.81(0.67–0.99)	-	-	-	0.69(0.56–0.85)	0.92(0.77–1.11)	-	96.2	92.7	74.8	60.8
KEYNOTE-042 in China^Citation23	128	134	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	0.62(0.38–1.00)	0.69(0.40–1.20)	-	-	-	-	-
KEYNOTE-189^Citation10	410	206	195	39	132	70	81	16	128	58	62	12	127	63	41	9	0.52(0.43–0.64)	0.36(0.25–0.52)	0.55(0.37–0.81)	0.75(0.53–1.05)	0.49(0.38–0.64)	0.42(0.26–0.68)	0.55(0.34–0.90)	0.59(0.38–0.92)	94.6	90.7	69.2	57.8
KEYNOTE-407^Citation13	278	281	161	108	73	73	44	24	103	104	51	43	95	99	60	40	0.56(0.45–0.70	0.37(0.24–0.58)	0.56(0.39–0.80)	0.68(0.47–0.98)	0.64(0.49–0.85)	0.64(0.37–1.10)	0.57(0.36–0.90)	0.61(0.38–0.98)	91.8	87.2	57.4	41.6
IMpower-130^Citation14	447	226	220	72	-	-	-	-	-	-	-	-	-	-	-	-	0.65(0.54–0.77)	0.51(0.34–0.77)	0.61(0.43–0.85)	0.72(0.56–0.91)	0.80(0.65–0.99)	0.84(0.51–1.39)	0.70(0.45–1.08)	0.81(0.61–1.08)	99.8	99	67.2	65.8
IMpower-131^Citation17,Citation21	169	140	83	57	32	16	19	5	67	53	35	23	70	71	31	30	0.71(0.60–0.85)	0.44(0.27–0.71)	0.70(0.53–0.92)	0.81(0.64–1.03)	0.88(0.73–1.05)	0.48(0.29–0.81)	1.08(0.81–1.45)	0.87(0.67–1.13)	98.2	97.9	69.8	68.2
IMpower-132^Citation18	292	286	-	-	-	-	-	-	-	-	-	-	-	-	-	-	0.60(0.494–0.72)	0.46(0.22–0.96)	0.80(0.56–1.16)	0.45(0.31–0.64)	0.81(0.64–1.03)	-	-	-	93.2	90.3	39	22.6
IMpower-150^Citation16,Citation22	359	337	-	-	74	71	51	35	134	126	78	51	189	196	95	72	0.59(0.5–0.69)	0.33(0.22–0.51)	0.55(0.42–0.73)	0.75(0.60–0.94)	0.76(0.63–0.93)	0.67(0.42–1.06)	0.76(0.54–1.08)	0.83(0.64–1.08)	62.7	89.9	17.8	41
	349	337	-	-	68	71	42	35	147	126	64	51	185	196	57	72	0.91(0.78–1.06)	0.63(0.43–0.92)	0.79(0.61–1.03)	1.10(0.89–1.36)	0.85(0.71–1.03)	0.75(0.47–1.20)	0.74(0.52–1.03)	0.98(0.76–1.27)	73.4	90	26.6	53.3

Abbreviation: EM: experimental arm; CM: control arm; Pembro: pembrolizumab; Chemo: chemotherapy; Placebo+Chemo: placebo plus chemotherapy; PC: pembrolizumab plus chemotherapy; AC: atezolizumab plus chemotherapy; ABC: atezolizumab plus bevacizumab plus chemotherapy; BC: bevacizumab plus chemotherapy. NR: not reported; PFS: progression-free survival; OS: overall survival. HR: hazard ratio

Figure 1. Flow chart of study selection

Figure 2. Network structure for all the included trials. Each circular node represents a treatment type. The circle size is proportional to the total number of patients. The width of lines is proportional to the number of studies performing head-to-head comparisons in the same study, and the dotted line is the indirect comparison which was shown in this NWM

Figure 3. ORR, PFS, and OS profiles for study cohort in the subgroup analysis based on PD-L1 expression. PD-L1-high (a,b), PD-L1-intermediate (c,d) and PD-L1-negative (e,f) subgroup analysis according to network meta-analysis (NMA). Each cell contains the pooled odds ratios (OR) and 95% credibility intervals for ORR, and the Hazard-Radio (HR) and 95% credibility intervals for PFS and OS; significant results are emboldened

Figure 4. PFS and OS comparison profiles for non-squamous NSCLC under subgroup analysis are based on PD-L1 expression. PD-L1-high (a), PD-L1-intermediate (b) and PD-L1-negative (c) subgroup analysis according to network meta-analysis (NMA). Each cell contains the Hazard-Radio (HR) and 95% credibility intervals for PFS and OS; significant results are emboldened

Figure 5. ORR, PFS, and OS comparative profiles for PD-L1-high squamous NSCLC according to network meta-analysis (NMA). Each cell contains the pooled odds ratios (OR) and 95% credibility intervals for ORR (a), and the Hazard-Radio (HR) and 95% credibility intervals for PFS and OS (b); significant results are emboldened

Figure 6. Incidence of grade 1–5 AEs and grade ≥3 AEs comparative profiles according to network meta-analysis (NMA). Each cell contains the pooled odds ratios (OR) and 95% credibility intervals for the incidence of AEs; significant results are emboldened. AEs: adverse events AE

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Availability of data and materials

All data generated or analyzed during this study are included in this published article and its supplementary information files.