Table 4.

Trial- and individual patient–level surrogacy for subgroups for 5, 6, and 6.5 years of median follow-up, respectively^a

Subgroup and true endpoint	No. of comparison units (No. of patients)	${\mathrm{R}}_{\text{WLS}}^2$ (95% CI)	${\mathrm{R}}_{\text{Copula}}^2$ (95% CI)	ρCopula (95% CI)
Age <65 y
5-y OS	13 (12 943)	0.73 (0.52 to 0.94)	0.66 (0.37 to 0.96)	0.90 (0.90 to 0.91)
6-y OS	12 (11 382)	0.76 (0.51 to 1.00)	0.73 (0.46 to 0.99)	0.91 (0.90 to 0.91)
6.5-y OS	9 (7444)	0.83 (0.61 to 1.00)	0.81 (0.58 to 1.00)	0.91 (0.90 to 0.91)
Age $\ge$65 y
5-y OS	13 (6238)	0.71 (0.47 to 0.94)	0.56 (0.21 to 0.92)	0.91 (0.91 to 0.92)
6-y OS	12 (5540)	0.78 (0.60 to 0.95)	0.69 (0.41 to 0.98)	0.92 (0.91 to 0.92)
6.5-y OS	9 (3840)	0.75 (0.49 to 1.00)	0.69 (0.36 to 1.00)	0.91 (0.90 to 0.92)
KRAS WT
5-y OS	7 (5406)	0.86 (0.53 to 1.00)	0.95 (0.88 to 1.00)	0.91 (0.90 to 0.92)
6-y OS	6 (4856)	0.84 (0.39 to 1.00)	0.95 (0.87 to 1.00)	0.91 (0.90 to 0.92)
6.5-y OS	5 (4600)	0.85 (0.42 to 1.00)	0.96 (0.90 to 1.00)	0.91 (0.90 to 0.92)
KRAS MT
5-y OS	6 (2491)	0.90 (0.71 to 1.00)	0.93 (0.81 to 1.00)	0.90 (0.89 to 0.92)
6-y OS	5 (2133)	0.87 (0.46 to 1.00)	0.90 (0.74 to 1.00)	0.91 (0.89 to 0.92)
6.5-y OS	4 (2009)	0.90 (0.34 to 1.00)	0.97 (0.91 to 1.00)	0.91 (0.89 to 0.92)
BRAF WT
5-y OS	9 (7979)	0.70 (0.27 to 1.00)	0.71 (0.39 to 1.00)	0.89 (0.88 to 0.90)
6-y OS	8 (7142)	0.78 (0.38 to 1.00)	0.78 (0.51 to 1.00)	0.89 (0.88 to 0.90)
6.5-y OS	7 (5985)	0.83 (0.27 to 1.00)	0.80 (0.53 to 1.00)	0.89 (0.88 to 0.90)
BRAF MT
5-y OS	7 (1095)	0.92 (0.78 to 1.00)	0.94 (0.86 to 1.00)	0.96 (0.95 to 0.97)
6-y OS	6 (1018)	0.94 (0.80 to 1.00)	0.96 (0.89 to 1.00)	0.96 (0.95 to 0.97)
6.5-y OS	5 (856)	0.92 (0.78 to 1.00)	0.96 (0.88 to 1.00)	0.96 (0.95 to 0.97)
High risk
5-y OS	14 (8662)	0.60 (0.30 to 0.90)	0.56 (0.22 to 0.91)	0.89 (0.89 to 0.90)
6-y OS	13 (7661)	0.59 (0.28 to 0.90)	0.60 (0.27 to 0.94)	0.90 (0.89 to 0.90)
6.5-y OS	10 (5070)	0.68 (0.34 to 1.00)	0.65 (0.29 to 1.00)	0.89 (0.89 to 0.90)
Low risk
5-y OS	12 (10 153)	0.64 (0.35 to 0.93)	0.60 (0.25 to 0.95)	0.90 (0.90 to 0.91)
6-y OS	11 (8896)	0.69 (0.43 to 0.94)	0.65 (0.32 to 0.98)	0.91 (0.90 to 0.92)
6.5-y OS	8 (5863)	0.73 (0.47 to 0.99)	0.64 (0.24 to 1.00)	0.91 (0.90 to 0.92)
dMMR
5-y OS	6 (933)	0.86 (0.67 to 1.00)	0.96 (0.91 to 1.00)	0.93 (0.92 to 0.95)
6-y OS	5 (828)	0.87 (0.49 to 1.00)	0.94 (0.83 to 1.00)	0.93 (0.91 to 0.95)
6.5-y OS	4 (675)	0.90 (0.71 to 1.00)	0.97 (0.92 to 1.00)	0.93 (0.91 to 0.95)
pMMR
5-y OS	9 (7756)	0.64 (0.16 to 1.00)	0.78 (0.52 to 1.00)	0.90 (0.89 to 0.91)
6-y OS	8 (6995)	0.66 (0.19 to 1.00)	0.80 (0.54 to 1.00)	0.90 (0.89 to 0.91)
6.5-y OS	7 (6052)	0.80 (0.29 to 1.00)	0.79 (0.52 to 1.00)	0.90 (0.89 to 0.91)
Distal
5-y OS	11 (7277)	0.72 (0.51 to 0.93)	0.65 (0.32 to 0.98)	0.88 (0.87 to 0.89)
6-y OS	10 (5885)	0.75 (0.45 to 1.00)	0.62 (0.25 to 0.99)	0.88 (0.87 to 0.89)
6.5-y OS	8 (4896)	0.85 (0.60 to 1.00)	0.80 (0.56 to 1.00)	0.88 (0.87 to 0.89)
Proximal
5-y OS	10 (5968)	0.67 (0.37 to 0.97)	0.54 (0.11 to 0.96)	0.92 (0.92 to 0.93)
6-y OS	9 (5116)	0.86 (0.74 to 0.98)	0.77 (0.51 to 1.00)	0.92 (0.92 to 0.93)
6.5-y OS	8 (4158)	0.86 (0.72 to 0.99)	0.77 (0.48 to 1.00)	0.93 (0.92 to 0.93)
Excluding IRI
5-y OS	11 (15 696)	0.81 (0.57 to 1.00)	0.71 (0.41 to 1.00)	0.91 (0.90 to 0.91)
6-y OS	11 (15 696)	0.87 (0.65 to 1.00)	0.89 (0.78 to 1.00)	0.90 (0.90 to 0.91)
6.5-y OS	8 (10 058)	0.96 (0.77 to 1.00)	0.97 (0.94 to 1.00)	0.90 (0.90 to 0.91)
Biologics
5-y OS	6 (6623)	0.82 (0.37 to 1.00)	0.97 (0.93 to 1.00)	0.90 (0.89 to 0.91)
6-y OS	6 (6623)	0.87 (0.41 to 1.00)	0.98 (0.95 to 1.00)	0.90 (0.89 to 0.91)
6.5-y OS	5 (4662)	0.94 (0.34 to 1.00)	1.00 (0.99 to 1.00)	0.90 (0.89 to 0.91)

^a CI = confidence interval; dMMR = deficient mismatch repair; IRI = irinotecan; MT = mutation; OS = overall survival; pMMR = proficient mismatch repair; WLS = weighted least squares; WT= wild-type; ρ_Copula = rank correlation coefficient.