Table 2.

Two-condition surrogacy analysis among patients with hormone-receptor positive/HER2-negative breast cancer.

ICE	Outcome-level surrogacy (OS and ICE are correlated irrespective of treatment)				Trial-level surrogacy (treatment effects on both end points are correlated)
	Correlation at the patient level		Regression of 8-year OS rate v 5-year ICE rate by trial, Arm, and nodal status (No. of units = 16)		Regression of Log (HR)-OS v Log (HR)-ICE by trial and nodal status (No. of units = 8)
	No. of events out of 6612 patients included	Kendall’s τ (95% CI)	No. of events out of 7718 patients included	R2 (95% CI)	R2 (95% CI)	Regression equation
DFS	1450	0.73 (0.72–0.75)	1855	0.92 (0.79–0.95)	0.54 (0.00–0.76)	Log (HR)OS = −0.158 + 0.666∗Log (HR)DFS
DDFS	1211	0.80 (0.79–0.82)	1566	0.92 (0.79–0.95)	0.67 (0.05–0.83)	Log (HR)OS = −0.110 + 0.811∗Log (HR)DDFS
RFS	1204	0.80 (0.79–0.82)	1558	0.94 (0.83–0.96)	0.66 (0.04–0.82)	Log (HR)OS = −0.109 + 0.756∗Log (HR)RFS
DRFS	1082	0.85 (0.84–0.86)	1413	0.94 (0.84–0.96)	0.67 (0.05–0.83)	Log (HR)OS = −0.082 + 0.791∗Log (HR)DRFS
IBCFS	1325	0.77 (0.75–0.78)	1707	0.94 (0.84–0.96)	0.49 (0.00–0.74)	Log (HR)OS = −0.147 + 0.617∗Log (HR)IBCFS
RFI	900	0.71 (0.69–0.73)	1206	0.95 (0.87–0.97)	0.49 (0.00–0.74)	Log (HR)OS = −0.114 + 0.531∗Log (HR)RFI
DRFI	767	0.76 (0.74–0.78)	1048	0.94 (0.85–0.97)	0.53 (0.00–0.75)	Log (HR)OS = −0.090 + 0.539∗Log (HR)DRFI
BCFI	1030	0.67 (0.65–0.69)	1365	0.95 (0.85–0.97)	0.29 (0.00–0.63)	Log (HR)OS = −0.158 + 0.400∗Log (HR)BCFI

DFS, disease-free survival; HR, hazard ratio; ICE, intermediate clinical end point; OS, overall survival; DDFS distant disease-free survival; RFS, recurrence-free survival; DRFS, distant relapse–free survival; RFI, recurrence-free interval; DRFI, distant recurrence-free interval; BCFI, breast cancer–free interval; IBCFS, invasive breast cancer–free survival.