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 6 Summary of arm-level sensitivity analysis (Spearman correlation)

Sensitivity Analysis	No. of arms	r_s	95%CI
*ORR ~ median OS*
Line of therapy
First-line	88	0.636	0.492, 0.746
≥ 2nd-line	146	0.611	0.498, 0.703
Phase of trial
Phase II	141	0.703	0.609, 0.762
Phase III	111	0.660	0.541, 0.754
Masking
Double-blind	66	0.629	0.456, 0.756
Open-label	186	0.710	0.631, 0.775
Therapy*
Targeted therapy-based	123	0.749	0.660, 0.818
Immunotherapy -based	54	0.449	0.207, 0.640
Chemotherapy-based	65	0.706	0.558, 0.810
Overall	254	0.700	0.631,0.758
*ORR ~ median PFS*
Line of therapy
First-line	93	0.699	0.578, 0.790
≥ 2nd-line	153	0.735	0.653, 0.801
Phase of trial
Phase II	153	0.825	0.768, 0.870
Phase III	117	0.790	0.711, 0.850
Masking
Double-blind	76	0.888	0.828, 0.927
Open-label	193	0.796	0.738, 0.842
Therapy*
Targeted therapy-based	132	0.823	0.759, 0.871
Immunotherapy -based	58	0.793	0.673, 0.873
Chemotherapy-based	68	0.783	0.669, 0.861
Overall	271	0.831	0.790,0.864
*median PFS ~ median OS*
Line of therapy
First-line	109	0.832	0.763, 0.882
≥ 2nd-line	177	0.599	0.495, 0.686
Phase of trial
Phase II	143	0.798	0.730, 0.851
Phase III	154	0.705	0.616, 0.777
Masking
Double-blind	83	0.727	0.606, 0.815
Open-label	221	0.755	0.692, 0.807
Therapy*
Targeted therapy-based	132	0.756	0.672, 0.821
Immunotherapy -based	76	0.656	0.506, 0.768
Chemotherapy-based	82	0.786	0.687, 0.857
Overall	306	0.755	0.702,0.799

Targeted therapy-based: including targeted therapy with or without placebo/normal care
Immunotherapy: including immunotherapy with or without placebo/normal care
Chemotherapy-based: including conventional chemotherapy with or without placebo/normal care

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