Indirect Analysis of First-Line Therapy for Advanced Non-Small-Cell Lung Cancer with Activating Mutations in a Japanese Population

Figures & data

Figure 1. PRISMA criteria.

Figure 2. Base case network diagram.

Non randomized data was defined as any post hoc subgroup data that broke randomization; LUX-Lung 3 and FLAURA reported post hoc Japanese subgroup results, however, the randomization was not stratified by Japanese ethnicity.

AFA: Afatinib; BEV: Bevacizumab; CICIS: Cisplatin; DAC: Dacomitinib; ERL: Erlotinib; GEF: Gefitinib; OSI: Osimertinib.

Table 1. Summary of study/patient characteristics and results of randomized controlled trials included across network meta-analyses.

Trial name	Arm	Sample size	Median age	Male (%)	ECOG PS 0 (%)	ECOG PS 1 (%)	Brain/CNS Metastases %	Stage IV (%)	Never smoker (%)	Exon 19 deletion mutation (%)	Exon 21 L858R mutation (%)
ARCHER 1050	DAC	40	66	38	70%	30%	–	95^†	48	65^†	35^†
	GEF	41	67	49	51	49	–	98^†	59	63^†	37^†
FLAURA	OSI	65	67	34	58	42	22	92	54	51	49
	GEF	55	67	49	62	38	24	96	53	55	45
JO25578	ERL	77	67	34	53	47	–	81	58	52	48
	ERL+BEV	75	67	40	57	43	–	80	56	53	47
LUX-Lung 3	AFA	54	66	31	50	50	19	89	59	43^¶	50^¶
	CIS+PEM	29	66	31	59	41	24	83	66	55^¶	38^¶
NEJ002	GEF	114	64‡	37	47^§	52^§	–	77	66	51^¶	43^¶
	CAR+PAC	114	63‡	36	50^§	48^§	–	74	58	52^¶	42^¶
NEJ026	ERL	112	68	35	61^§	38^§	32	75	57	49	51
	ERL+BEV	112	67	37	57^§	43^§	32	73	58	50	50
WJTOG3405	GEF	86	64	31	65	35	–	48	71	58	42
	CIS+DOC	86	64	30	60	40	–	48	66	43	57

† These data were extracted from a confidential Pfizer Study Report at the time of the SLR. These data have recently been published.

‡ Means reported in lieu of median.

§ ECOG PS 0 and ECOG PS 1 do not sum to 100% since a small proportion of the sample have ECOG PS=2.

¶ Proportions do not sum to 100% as other mutational statuses are reported in addition to deletion 19 and exon 21 mutation.

All values are rounded to the nearest whole number.

AFA: Afatinib; BEV: Bevacizumab; CAR: Carboplatin; CIS: Cisplatin; DAC: Dacomitinib; Del: Deletion; DOC: Docetaxel; ECOG PS: European Cooperative Oncology Group performance score; ERL: Erlotinib; GEF: Gefitinib; OSI: Osimertinib; PAC: Paclitaxel; PEM: Pemetrexed.

Table 2. Progression-free survival (independent review committee) relative efficacy hazard ratios and 95% credible intervals for all EGFR TKI comparisons in the base case network.

Treatment	Treatment HR (95% CrI)
	Afatinib	Platinum-based chemotherapy	Dacomitinib	Erlotinib+bevacizumab	Gefitinib/erlotinib	Osimertinib
Afatinib		3.58 (1.92–6.59)	0.74 (0.31–1.77)	0.79 (0.38–1.59)	1.37 (0.70–2.65)	0.83 (0.37–1.88)
Platinum-based Chemotherapy	0.28 (0.15–0.52)		0.21 (0.11–0.39)	0.22 (0.15–0.32)	0.38 (0.30–0.49)	0.23 (0.14–0.39)
Dacomitinib	1.36 (0.57–3.26)	4.85 (2.60–8.93)		1.06 (0.57–1.97)	1.85 (1.05–3.23)	1.13 (0.54–2.35)
Erlotinib+bevacizumab	1.27 (0.63–2.61)	4.57 (3.17–6.54)	0.94 (0.51–1.75)		1.74 (1.33–2.28)	1.06 (0.61–1.81)
Gefitinib/erlotinib	0.73 (0.38–1.43)	2.62 (2.05–3.33)	0.54 (0.31–0.96)	0.57 (0.44–0.75)		0.61 (0.38–0.98)
Osimertinib	1.21 (0.53–2.72)	4.31 (2.54–7.30)	0.88 (0.43–1.86)	0.94 (0.55–1.64)	1.64 (1.02–2.65)

Cells correspond to the relative effect of the column treatment vs row treatment. A hazard ratio of <1.0 indicates benefit in favor of the column treatment.

CrI: Credible interval; HR: Hazard ratio; TKI: Tyrosine kinase inhibitor.

Table 3. Progression-free survival rank probabilities for all EGFR TKIs in the base case network.

Treatment	Probability of being ranked first(%)
Afatinib	12.5
Platinum-based chemotherapy	0.0
Dacomitinib	43.3
Erlotinib+bevacizumab	22.5
Gefitinib/erlotinib	0.0
Osimertinib	21.7