Anti-angiogenic therapies for metastatic colorectal cancer: Current and future perspectives

Table 1 Clinical trials and main anti-angiogenic drugs in metastatic disease

Clinical trial	Phase	Line	Regimen	Median PFS (mo)	Median OS (mo)	ORR (%)
Aflibercept
VELOUR NCT00561470[87]	III	2nd	FOLFIRI + aflibercept vs FOLFIRI + placebo	6.90 vs 4.67 HR = 0.758, P = 0.0001	13.50 vs 12.06 HR = 0.817, P = 0.0032	19.8 vs 11.1 P = 0.001
AFFIRM NCT00851084[86]	II	1st	mFOLFOX6 + aflibercept vs mFOLFOX6	8.48 vs 8.77		49.1 vs 45.9
Brivanib
NCT00640471[90]	III	3rd	Cetuximab + brivanib vs cetuximab + placebo	5.0 vs 3.4 HR = 0.72, P < 0.001	8.8 vs 8.1 HR = 0.88, P = 0.12	13.6 vs 7.2 P = 0.004
Regorafenib
CORRECT NCT01103323[99]	III	2nd	Regorafenib vs placebo	1.9 vs 1.7 HR = 0.49, P < 0.000001	6.4 vs 5.0 HR = 0.77, P = 0.0052
Sorafenib
RESPECT NCT00865709[107]	II	1st	mFOLFOX6 + sorafenib vs mFOLFOX6 + placebo	9.1 vs 8.7 HR = 0.88, P = 0.46	17.6 vs 18.1 HR = 1.13, P = 0.51
Sunitinib
NCT00668863	II	1st
NCT00457691[108]	III	1st	FOLFIRI + sunitinib vs FOLFIRI + placebo	7.8 vs 8.4 HR = 1.095, P = 0.807	20.3 vs 19.8 HR = 1.171, P = 0.916	32 vs 34 P = 0.683
Valatanib
CONFIRM1 NCT00056459[110]	III	1st	FOLFOX4 + vatalanib vs FOLFOX4 + placebo	7.7 vs 7.6 HR = 0.88, P = 0.118	21.4 vs 20.5 HR = 1.08, P = 0.260	P > 0.05
CONFIRM 2 NCT00056446[111]	III	2nd	FOLFOX4 + vatalanib vs FOLFOX4 + placebo	5.6 vs 4.2HR = 0.83, P = 0.013	13.1 vs 11.9HR = 1.00, P = 0.957

mCRC: Metastatic colorectal cancer; PFS: Progression-free-survival; OS: Overall survival; ORR: Overall response rate; FOLFIRI: 5-fluorouacil + leucovorin + irinotecan; mFOLFOX6: 5-fluoroaucil + leucovorin + oxaliplatin; HR: Harzard ratio.