Table 2.

Subgroup surrogacy analysis of intermediate clinical endpoints.

	Trials, n	Comparisons, n	Sample size, n	Correlation of treatment effects (R2, 95% CI)
				RROR vs. HROS	RRDC vs. HROS	HRPFS vs. HROS	Ratio1y-OS vs. HROS
Tumour types
Lung cancer	29	34	19,006	0.11 (0.00–0.36)	0.01 (0.00–0.14)	0.25 (0.03–0.53)	0.81 (0.64–0.90)
GC/GEJC/EC	9	12	6482	0.52 (0.06–0.84)	0.52 (0.05–0.85)	0.56 (0.09–0.86)	0.79 (0.41–0.94)
Urothelial cancer	5	7	4215	0.51 (0.01–0.91)	0.47 (0.02–0.90)	0.44 (0.01–0.68)	0.78 (0.15–0.97)
Masking
Open-label	54	65	37,336	0.14 (0.02–0.32)	0.00 (0.00–0.08)	0.45 (0.25–0.63)	0.71 (0.57–0.81)
Double-blind	22	23	14,750	0.05 (0.00–0.36)	0.14 (0.00–0.54)	0.53 (0.20–0.77)	0.81 (0.60–0.92)
Line of treatment
1	50	60	36,339	0.09 (0.02–0.25)	0.00 (0.00–0.09)	0.32 (0.12–0.52)	0.70 (0.54–0.81)
>1	26	28	15,254	0.17 (0.00–0.46)	0.00 (0.00–0.18)	0.57 (0.28–0.78)	0.85 (0.69–0.92)
Treatment strategy
Monotherapy	37	37	21,154	0.25 (0.00–0.52)	0.02 (0.00–0.23)	0.53 (0.24–0.74)	0.84 (0.70–0.91)
Combination treatment	48	52	32,850	0.02 (0.01–0.15)	0.01 (0.00–0.14)	0.39 (0.17–0.59)	0.67 (0.49–0.81)
Drug target
PD-1	42	44	26,480	0.13 (0.01–0.36)	0.25 (0.04–0.51)	0.57 (0.35–0.74)	0.74 (0.56–0.85)
PD-L1	28	30	18,262	0.11 (0.00–0.38)	0.05 (0.00–0.30)	0.43 (0.14–0.69)	0.79 (0.61–0.89)
PD-1/PD-L1+CTLA-4	11	11	6794	0.00 (0.00–0.41)	0.36 (0.00–0.81)	0.40 (0.00–0.85)	0.25 (0.00–0.75)
Median follow-up
>24 months	43	52	30,221	0.22 (0.03–0.46)	0.35 (0.10–0.60)	0.40 (0.15–0.63)	0.72 (0.52–0.84)
≤24 months	33	35	21,298	0.03 (0.00–0.24)	0.02 (0.00–0.23)	0.63 (0.41–0.81)	0.78 (0.60–0.89)

CI, confidential interval; CTLA-4, cytotoxic T lymphocyte antigen-4; DC, disease control; EC, oesophageal cancer; GC, gastric cancer; GEJC, gastroesophageal junction cancer; HR, hazard ratio; OR, objective response; OS, overall survival; PD-1, programmed death-1; PD-L1, programmed death ligand 1; PFS, progression-free survival; RR, relative risk.