Validating ORR and PFS as surrogate endpoints in phase II and III clinical trials for NSCLC patients: difference exists in the strength of surrogacy in various trial settings

Table 8 Summary of trial-level sensitivity analysis (Linear regression)

Sensitivity Analysis	No. of trials	Slope estimate	95%CI	R²	Adjusted R²	Threshold
*ΔORR ~ HR of OS*^a
Line of therapy
First-line	39	0.019	0.013, 0.024	0.570	0.558	−28.01%
≥ 2nd-line	64	0.008	0.004, 0.012	0.166	0.153	——^b
Phase of trial
Phase II	60	0.010	0.406, 0.014	0.294	0.282	——^b
Phase III	52	0.012	0.007, 0.018	0.267	0.252	——^b
Masking
Double-blind	35	0.016	0.009, 0.023	0.365	0.345	——^b
Open-label	76	0.007	0.004, 0.011	0.176	0.165	——^b
Overall	112	0.011	0.007, 0.014	0.261	0.254	——^b
*ΔORR ~ HR of PFS*^a
Line of therapy
First-line	36	0.023	0.018, 0.029	0.641	0.630	−23.25%
≥ 2nd-line	68	0.023	0.018, 0.029	0.528	0.521	−29.95%
Phase of trial
Phase II	60	0.023	0.018, 0.028	0.588	0.581	−35.82%
Phase III	54	0.023	0.017, 0.028	0.568	0.560	−19.28%
Masking
Double-blind	36	0.018	0.012, 0.025	0.468	0.453	−33.76%
Open-label	77	0.025	0.021, 0.030	0.640	0.636	−24.42%
Overall	114	0.023	0.019, 0.027	0.578	0.574	−26.30%
*HR of PFS^a ~ HR of OS*^a
Line of therapy
First-line	48	0.555	0.419, 0.691	0.580	0.571	0.49
≥ 2nd-line	81	0.333	0.217, 0.449	0.286	0.277	——^b
Phase of trial
Phase II	62	0.374	0.255, 0.492	0.390	0.380	——^b
Phase III	72	0.427	0.302, 0.553	0.390	0.382	0.41
Masking
Double-blind	42	0.793	0.610, 0.977	0.642	0.633	0.48
Open-label	95	0.276	0.178, 0.374	0.246	0.238	——^b
Overall	138	0.403	0.313, 0.494	0.360	0.355	——^b

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