Advances and new perspectives in the treatment of metastatic colon cancer

Table 1 Selected phase 3 clinical trials involving anti-angiogenic drugs in combination with conventional chemotherapy

Ref.	Drug and study name	Study description	No. of patients	Comparison	Median OS (mo)	Median TTP/PFS (mo)	ORR	1-yr survival
	Bevacizumab (B)
Hurwitz et al[8] 2004	AVF2107g trial	RCT, 1st line	813 (ITT)	IFL + B vs IFL	20.3 vs 15.6	10.6 vs 6.2	45% vs 35%	74% vs 63%
Fuchs et al[10] 2007	BICC-C trial	RCT, 1st line	117 (2nd period)	FOLFIRI + B vs mIFL + B	28 vs 19	11 vs 8	58% vs 53%	87% vs 61%
Giantonio et al[12] 2007	ECOG 3200 trial	RCT, 2nd line post irinotecan 1st line	820 (ITT)	FOLFOX-4 + B vs FOLFOX-4 vs B alone	12.9 vs 10.8 vs 10.2	7.3 vs 4.7 vs 2.7	23% vs 8.6% vs 3.3%	56% vs 43% vs 44%
Saltz et al[13] 2008	NO16966 trial	RCT, phase 3, 1st line, factorial 2 x 2	1401	FOLFOX-4 or XELOX + B vs FOLFOX-4 or XELOX	21.3 vs 19.9	9.4 vs 8.0	47% vs 49%	Not reported
Tebbutt et al[17] 2010	MAX trial	RCT, open label, 1st line	471	Cape alone vs Cape + B vs Cape + B + mitomycin	18.9 18.9 vs 16.4	5.7 vs 8.5 vs 8.4	30% vs 38% vs 46%	Not reported
Cunningham et al[18] 2013	AVEX trial	RCT, elder population, 1st line	280	Cape alone vs Cape + B	20.7 vs 16.8	9.1 vs 5.1	19% vs 10%	74% vs 44%
Falcone et al[21] 2013	TRIBE trial	RCT, 1st line	508	FOLFOXIRI-B vs FOLFIRI-B	31.0 vs 25.8	12.1 vs 9.7	65% vs 53%	Not reported
Bennouna et al[66] 2013	ML 18147	RCT, open label, 2nd line post chemo + B	409	2nd line chemotherapy + B vs 2nd line chemotherapy	11.2 vs 9.8	5.7 vs 4.1	5.5% vs 4%	Not reported (approximately 50% vs 40%)
	Ziv-Aflibercept
Van Cutsem et al[29] 2012	VELOUR trial	RCT, 2nd line post oxaliplatin and/or bevacizumab 1st line	1226	FOLFIRI + aflibercept vs FOLFIRI + placebo	13.5 vs 12.0	6.9 vs 4.7	20% vs 11%	56% vs 50%

RCT: Randomized controlled trial; OS: Overall survival; TTP: Time to progression; PFS: Progression free survival; ITT: Intention to treat; ORR: Overall response rate.