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.

Table 2 Selected clinical trials involving anti-epidermal growth factor receptor, regorafenib or anti-epidermal growth factor receptor vs anti-epidermal growth factor receptor receptor agents

Ref.	Drug and study name	Study description	No. of patients	Comparison	Median OS (mo)	Median TTP/PFS (mo)	ORR	1-yr survival
	Cetuximab (C)
Cunningham et al[34] 2004	BOND trial	RCT, phase 2, 2nd line irinotecan-refractory	329	Irinotecan + C vs irinotecan	8.6 vs 6.9	4.1 vs 1.5	23% vs 11%	29% vs 32%
Van Cutsem et al[37] 2009	CRYSTAL trial	RCT, 1st line	1198	FOLFIRI + C vs FOLFIRI	20 vs 18.5 and (25 vs 21)	9 vs 8 and (10 vs 8.7)	47% vs 39% (59 vs 43%)	Not reported (approximately 35% vs 25%)
Maughan et al[59] 2011	COIN trial	RCT, phase 3, 1st line	729 (KRAS wild type)	Oxaliplatin-based chemo + C vs chemo alone	17 vs 17.9	8.6 vs 8.6	64% vs 57%	Not reported
Tveit et al[60] 2011	NORDIC VII trial	RCT, open label, 1st line	571	FLOX + C vs intermittent FLOX + C vs FLOX	19.7 vs 20.3 vs 20.4	8.3 vs 7.3 vs 7.9	49% vs 47% vs 41%	Not reported (approximately 70%)
	Panitumumab (P)
Douillard et al[39] 2010	PRIME trial	RCT, phase 3, 1st line	1183	FOLFOX-4 + P vs FOLFOX-4	24 vs 20 (WT) 15 vs 19 (MT)	9.6 vs 8 (WT) 7.3 vs 8.8 (MT)	55 vs 48% (WT) 40 vs 40% (MT)	Approximately 75% both (WT) approximately 60% vs 75% (MT)
	Regorafenib (R)
Grothey et al[47] 2013	CORRECT trial	RCT, phase 3, 3rd line	760	Regorafenib vs placebo	6.4 vs 5.0	1.9 vs 1.7	1.0% vs 0.4%	24.3% vs 20.0%
	Cetuximab (C) vs Bevacizumab (B)
Stintzing et al[63] 2013	FIRE-3trial	RCT, phase 3, 1st line	592	FOLFIRI + C vs FOLFIRI + B	28.7 vs 25	10 vs 10.3	62 % vs 58%	Not reported

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