Table 1.

Trial characteristics of the analyzed randomized controlled trials

Trial name	Trial characteristics
	Phase	Treatment line	Control arm	Escalation arm(s)	Target	Randomized	Tumors collected	With RAS wildtype	With RAS mutated
TRIBE	III	First line	FOLFIRI + Bevacizumab	FOLFOXIRI + Bevacizumab	Chemotherapy	508	391	93	236
AVG2107g	III	First line	IFL	IFL + Bevacizumab	Anti angiogenic	813	230	152	78
FOCUS	III	First line	5-FU	IrFU; OxFU	Chemotherapy	2 135	711	389	300
ML22011	III	First line	FP + Bevacizumab + Irinotecan	FP + Bevacizumab followed by Irinotecan	Chemotherapy	421	374	158	194
AGITG-MAX	III	First line	Capecitabine	Capecitabine + Bevacizumab(+ Mitomycin)	Anti angiogenic	471	280	171	109
ML18147	III	Second line	Chemotherapy	Chemotherapy + Bevacizumab	Anti angiogenic	820	616	316	300
RAISE	III	Second line	FOLFIRI	FOLFIRI + Ramucirumab	Anti angiogenic	1 076	1 072	542	530
VELOUR	III	Second line	FOLFIRI	FOLFIRI + Aflibercept	Anti angiogenic	1 226	482	218	264
CORRECT	III	Later line	Placebo	Regorafenib	Anti angiogenic	753	729	299	430
CONCUR	III	Later line	Placebo	Regorafenib	Anti angiogenic	204	143	79	64
RECOURSE	III	Later line	Best supportive care	Best supportive care + TAS102	Chemotherapy	800	800	393	407
AIOKRK0207	III	Maintenance	No treatment	Bevacizumab	Anti angiogenic	472	335	141	172
CAIRO3	III	Maintenance	No treatment	Capecitabine + Bevacizumab	Chemotherapy	558	420	140	240
PRODIGE 9	III	Maintenance	No treatment	Bevacizumab	Anti angiogenic	491	375	202	173

RAS rat sarcoma, FOLFIRI 5-fluorouracil/folinic acid/irinotecan, FOLFOXIRI 5-fluorouracil/folinic acid/oxaliplatin/irinotecan, IFL irinotecan/5-fluorouracil/folinic acid, VEGF vascular endothelial growth factor, 5-FU 5-fluorouracil, IrFU irinotecan/5-fluorouracil, OxFU oxaliplatin/5-fluorouracil, FP fluoropyrimidine, TAS102 trifluridin/tipiracil, EGFR epidermal growth factor receptor, ctDNA circulating tumor DNA