Table 3. Trials evaluating antiangiogenic agents in combination with EGFR TKIs in advanced NSCLC.

Study	Design	Patients	n	Study arm	Control arm	mPFS/mTTP	mOS	ORR	PE (P)
First-line
Ichihara et al. [78]	Phase II	NSCLC	42	Gef+Bev		14.4 m	Immature	73.8%	1-year PFS: 56.7%
JO25567 [76]	Phase II	NSCLC	154	Erl+Bev	Erl	16.0 vs 9.7 m	Immature	69% vs 64%	PFS; p = 0.0015
BELIEVE [77]	Phase II	NSCLC	109	Erl+Bev		13.8 m	Immature	76.1%	PFS
RELAY[83]	Phase Ib/III	Ongoing
Maintenance
ATLAS [79]	Phase III	NSCLC	1,155	Chemo+Bev→Bev+Erl	Chemo+Bev→Bev+Plac	4.8 vs 3.7 m	14.4 vs 13.3 m		PFS; p < 0.001
Second-line
Herbst et al. [37]	Phase II	nsNSCLC	81	Erl+Bev	Doc/Pem	4.4 m vs 3.0 m	13.7 vs 8.6m	17.9% vs 12.2%	PFS; HR: 0.72; 95%CI: 0.42-1.23
Beta [80]	Phse III	NSCLC	636	Erl+Bev	Erl+Plac	3.4 vs 1.7m	9.3 vs 9.2 m	13% vs 6%	OS; p = 0.758
Groen et al. [85]	Phase II	NSCLC	132	Sun+Erl	Sun+Plac	2.8 vs 2.0 m	8.2 vs 7.6 m	4.6% vs 3.0%	PFS; p = 0.321
Scagliotti et al. [86]	Phase III	NSCLC	960	Sun+Erl	Sun+Plac	3.6 vs 2.0 m	9.0 vs 8.5 m	10.6% vs 6.9%	OS; p = 0.1388
Spigel et al. [84]	Phase II	NSCLC	168	Sor+Erl	Erl+Plac	3.38 vs 1.94 m	7.62 vs 7.23 m	8% vs 11%	ORR (p = 0.56); PFS (p = 0.196)

NSCLC: non-small cell lung cancer; nsNSCLC: non-squamous non-small cell lung cancer; mPFS: median progression-free survival; mTTP: median time to progression; ORR: objective response rate; PE: Primary endpoint; Gef: gefitinib; Bev: bevacizumab; Erl: erlotinib; Sun: sunitinib; Plac: placebo; Doc: docetaxel; Pem: pemetrexed