Table 1. Study Characteristics.

Trial name	Line of therapy	Author, year	Experimental arm(s)	Standard arm	# pts.	MERGE Quality
Studies evaluating the addition of biological therapy to standard treatment
EGFR-I second line
Study 181	2	Peeters et al, 2010	Panitumumab + FOLFIRI	FOLFIRI	597	A
PICCOLO	2	Seymour et al, 2013	Panitumumab + Irinotecan	Irinotecan	460	A
EGFR-I third line+
CO.17	3+	Karapetis et al, 2008	Cetuximab	BSC	243 (KRAS WT)	A
	3+	Amado et al, 2008	Panitumumab	BSC	230 (KRAS WT)	A
Anti-VEGF second line
E3200	2	Giantonio et al, 2007	Bevacizumab +FOLFOX	FOLFOX	577	A
TML	2	Arnold, 2012	Bevacizumab + FOLFOX/FOLFIRI	FOLFOX/FOLFIRI	820	A
VELOUR	2	Van Cutsem et al, 2012	Aflibercept+FOLFIRI	FOLFIRI	1226	A
BEBYP	2	Masi et al, 2013	Bevacizumab + FOLFOX/FOLFIRI	FOLFOX/FOLFIRI	184	B2
CONFIRM2	2	Van Cutsem et al, 2011	Vatalanib (PTK/ZK) + FOLFOX	FOLFOX	855	A
Anti-VEGF third line+
CO.20	3+	Siu et al, 2013	Brivanib + Cetuximab	Cetuximab	750	A
CORRECT	3+	Grothey et al, 2013	Regorafenib	BSC	760	A
Agents against multiple/ novel targets
	2+	Yang et al, 2009	Vandetanib 300 + FOLFOX, Vandetanib 100 +FOLFOX	FOLFOX6	104	B1
	2+	Eng et al, 2011	Ganitumumab + Panitumumab, Rilotumumab + Panitumumab,	Panitumumab	142	B2
	3+	Watkins et al, 2011	Dalotuzumab 15 + Cetuximab + Irinotecan, Dalotuzumab 10 + Cetuximab + Irinotecan,	Cetuximab+ Irinotecan	345	B1
	2+	Cohn et al, 2013	Conatumumab + FOLFIRI, Ganitumab + FOLFIRI	FOLFIRI	155	A
	2	Eng et al, 2013	Tivatinib + Cetuximab + Irinotecan	Cetuximab + Irinotecan	117	B1
	2	Hoehler et al, 2013	Sorafenib	Placebo	97	B1
Studies comparing combination of chemotherapy with one targeted agent to combination with another targeted agent
	2	Bendell, 2011	Axitinib + FOLFOX/FOLFIRI	Bevacizumab + FOLFOX/FOLFIRI	171	B1
HORIZONI	2	Cunningham et al, 2004	Cediranib 20 + FOLFOX, Cediranib 30 + FOLFOX	Bevacizumab + FOLFOX	210	A
SPIRITT	2	Hecht et al, 2012	Panitumumab + FOLFIRI	Bevacizumab + FOLFIRI	182	B1