Table 3.

Approved anti-angiogenic agents: main trials results after the first-line.

Trial (phase)	Line	Treatment arms (n.)	Primary endpoint	PFS	OS	ORR (%)
E3200 (III) [50]	2nd	FOLFOX4 + bevacizumab (n.286) FOLFOX4 + placebo (n.291) Bevacizumab (n.243) prematurely closed due to futility	OS	7.3 m 4.7 m [HR 0.61; 95% CI, 0.51–0.73; p < 0.0001]	12.9 m 10.8 m [HR 0.75; 95% CI, 0.63–0.89; p = 0.0011]	22.7 8.6 [p < 0.0001]
TML (ML1847) (III) [54]	2nd	FOLFOX/FOLFIRI + bevacizumab (n.409) FOLFOX/FOLFIRI + placebo (n.411)	OS	5.7 m 4.1 m [HR 0.68; 95% CI, 0.59–0.68; p < 0.0001]	11.2 m 9.8 m [HR 0.81; 95% CI, 0.69–0.94; p = 0.0006]	5.4 3.9 *
VELOUR (III) [16]	2nd	FOLFIRI + aflibercept (n.612) FOLFIRI + placebo (n.614)	OS	6.9 m 4.7 m [HR 0.76; 95% CI, 0.66–0.87; p < 0.0001]	13.5 m 12.0 m [HR 0.82; 95% CI, 0.71–0.94; p = 0.032]	19.8 11.1 [p < 0.0001]
RAISE (III) [19]	2nd	FOLFIRI + ramucirumab (n.536) FOLFIRI + placebo (n.536)	OS	5.7 m 4.5 m [HR 0.79; 95% CI, 0.70–0.90; p = 0.0005]	13.5 m 12.0 m [HR 0.82; 95% CI, 0.71–0.94; p = 0.0219]	13.4 12.5 [p = 0.6336]
CORRECT (III) [21]	After 2nd	regorafenib + BSC (n.505) placebo + BSC (n.255)	OS	1.9 m 1.7 m [HR 0.49; 95% CI, 0.42–0.58; p < 0.0001]	6.4 m 5.0 m [HR 0.77; 95% CI, 0.64–0.94; one-sided p = 0.0052]	1 0.4 [p =0.19]

C: confidence interval; HR: hazard ratio; m: months; n: number of patients; PFS: progression free survival; ORR: objective response rate; OS: overall survival.

^*p = not reported.