Recurrence-free survival as a putative surrogate for overall survival in phase III trials of curative-intent treatment of colorectal liver metastases: Systematic review

Table 3 Comparison of original planned and analyzed design of randomized clinical trials with patients who underwent surgery and additional chemotherapy for initially resectable colorectal liver metastases

Studies	Initial design			No. of patients				Chemotherapy			%	Median FU		RFS		OS
by author	Primary endpoint	Planned HR	Type of analyses	Plan-ned	Acc-rued	ITT enrolled	PP (weight)	Regimen	Std Arm	Exp Arm	Resected	Std Arm	Exp Arm	Std Arm	Exp Arm	Std Arm	Exp Arm
Langer	OS	NR	PP	NR	129	129	107 (9)	Adj	0	5-FU × 6	100%	NR	NR	20	39	43 median	53 median
Portier	RFS	20% abs dif 2 yr1	ITT	200	173	171	171 (15)	Adj	0	5-FU × 6	100%	87.4	87.4	17.6	24.4	46.4 median	62.1 median
Nord-linger	RFS	0.714	Both	NR	364	364	342 (29)	Periop	0	FOLFOX × 12	93%	8.7 yr	8.7 yr	20	12.5	54.3	61.3
Ychou	RFS	NR	PP	420	321	321	306 (26)	Adj	1 5FU	FOLFIRI × 6	100%	42.4	41.7	21.6	24.7	72% at 3-yr	73% at 3-yr
Pri-mrose	RFS	0.68	ITT	268	272	257	236 (20)	Periop	FOL-FOX	Cetux + FOLFOX (70%)	85% (Chemo)	21.1	19.8	14.1	20.5	39.1	NR
											82% (Cetux)

¹Absence of difference at 2-year. HR: Hazard ratio; OS: Overall survival; RFS: Recurrence free survival; ITT: Intention to treat; PP: Per protocol; Std: Standard; Exp: Exposed; Adj: Adjuvant; Periop: Perioperative; 5-FU: 5-Fluorouracil; FOLFOX: 5-FU + Leucovorin + Oxaliplatin; FOLFIRI: 5-FU + Leucovorin + irirnotecan; Cetux: Cetuximab; Chemo: Chemotherapy; NR: Non-reported.