Table 2.
Selected randomized studies of VEGF inhibition in advanced non-small-cell lung cancer.
| Study (year) | Patient population | Study arms | PFS | OS | Ref. |
|---|---|---|---|---|---|
| Bev | |||||
| E4599 USA (2006) | n = 878; first-line nonsquamous NSCLC, no brain metastases, hemoptysis or therapeutic anticoagulation | Carbo/paclitaxel × 6 cycles ± concurrent Bev followed by maintenance | Carbo/paclitaxel + Bev − 6.2 months; Carbo/paclitaxel − 4.5 months; p< 0.001; S | Carbo/paclitaxel + Bev − 12.3 months; Carbo/paclitaxel − 10.3 months; p< 0.001; S | [38] |
| AVAiL Europe (2009) | n = 1043; first-line nonsquamous NSCLC, no brain metastases, hemoptysis or therapeutic anticoagulation | Cis/Gem × 6 cycles ± concurrent Bev followed by maintenance | Cis/Gem – Bev 6.5 m and 6.7 months; Cis/Gem − 6.1 months; p = 0.003, p = 0.03;NS | Cis/Gem + Bev −13.6 m and 13.4 months; Cis/Gem − 13.1 months; p = 0.42, p = 0.761; NS | [41] |
| AVAPERL Europe Preliminary report (2011) | n = 253; first-line nonsquamous NSCLC, no brain metastases, hemoptysis or therapeutic anticoagulation | Cis/Pem/Bev − 4 cycles followed by maintenance Bev ± Pern | Maintenance Pem/Bev− 10.2 m Maintenance Bev− 6.6 months; p< 0.001; S | Not yet mature | [104] |
| ATLAS USA Preliminary report (2010) | n = 768; first-line nonsquamous NSCLC, no brain metastases, hemoptysis or therapeutic anticoagulation | Platinum doublet/Bev × 4 cycles followed by maintenance Bev ± erlotinib | Maintenance Bev + placebo − 3.7 months; Maintenance Bev + erlotinib − 4.8 months; p = 0.0012; S | Bev + placebo − 13.3 months; Bev + erlotinib − 14.4 months; p = 0.56; NS | [42] |
| POINTBREAK USA Preliminary report (2012) | n = 939; first-line nonsquamous NSCLC, no brain metastases, hemoptysis or therapeutic anticoagulation | Carbo/Pem/Bev ×4→ maintenance Pem/Bevvs Carbo/taxol/Bev → maintenance Bev | Carbo/Pem/Bev − 6 months; Carbo/taxol/Bev − 5.6 months; p = 0.012; S | Carbo/Pem/Bev − 12.8 months; Carbo/taxol/Bev− 13.4 months; p = 0.949; NS | [108] |
| VEGF-targeted TKls | |||||
| BR24 Americas/Europe/Australasia (2009) | n = 296; first-line NSCLC, unselected | Carbo/paclitaxel × 6–8 cycles ± cediranib p.o. daily | Carbo/paclitaxel + cediranib − 5.6 months; Carbo/paclitaxel − 5 months; p = 0.13; NS | Carbo/paclitaxel + cediranib − 10.5 months; Carbo/paclitaxel − 10.1 months; p = 0.11; NS | [43] |
| NexUS Europe (2012) | n = 772; first-line NSCLC (squamous patients excluded from analysis) | Cis/Gem × 6 cycles ± sorafenib | Cis/Gem + sorafenib − 6 months; Cis/Gem − 5.5 months; p = 0.008 | Cis/Gem + sorafenib − 12.4 months; Cis/Gem − 12.5 months; p = 0.40; NS | [44] |
| SUN 1087 Europe/Asia (2012) | n = 960; second or subsequent line NSCLC, unselected | Erlotinib ± sunitinib | Erlotinib + sunitinib − 3.6 months; erlotinib − 2 months; p = 0.0023; S | Erlotinib + sunitinib − 9.0 months; erlotinib − 8.5 months; p = 0.14; NS | [45] |
| ZODIAC USA/Asia/Europe (2010) | n = 1391; second-line NSCLC | Docetaxel ±vandetanib | Docetaxel + vandetanib − 4 months; docetaxel − 3.2 months; p< 0.0001; S | Docetaxel + vandetanib − 10.3 months; docetaxel −9.9 months; p = 0.371; NS | [46] |
| ZEAL Europe/Australia (2011) | n = 434; second line, unselected | Pern ± vandetanib | Pern + vandetanib − 4.4 months; Pern − 3 months; p = 0.108; NS | Pern + vandetanib − 10.5 months; Pern − 9.2 months; p = 0.219; NS | [47] |
| ZEPHYR Asia (2012) | n = 924; second-line or subsequent line NSCLC, unselected | Vandetanib vs placebo | Vandetanib− 1.9 months; placebo − 1.8 months; p< 0.001; S | Vandetanib − 8.5 months; Placebo − 1.8 months; p = 0.527; NS | [48] |
| MONET1 Europe/Asia/USA (2012) | n = 1090; first-line nonsquamous | Carbo/paclitaxel ± motesanib | Carbo/paclitaxel + motesanib− 5.6 months; Carbo/paclitaxel − 5.4 months; p< 0.001; S | Carbo/paclitaxel + motesanib− 13 months; Carbo/paclitaxel − 11 months; p = 0.14; NS | [49] |
| Other VEGFIvasculature-targeted agents | |||||
| VITAL Europe/Americas (2012) | n = 913; second-line nonsquamous | Docetaxel ± aflibercept | Docetaxel + aflibercept − 5.2 months; docetaxel − 4.1 months; p = 0.0035; S | Docetaxel + aflibercept− 10.1 months; docetaxel − 10.4 months; p = 0.9; NS | [50] |
| ATTRACT-1 USA/Asia/Europe (2011) | n= 1299; first-line NSCLC; unselected | Carbo/paclitaxel ± ASA404 | Carbo/paclitaxel + ASA404− 5.5 months; Carbo/paclitaxel − 5.5m; p = 0.727; NS | Carbo/paclitaxel + ASA404 − 13.4 months; Carbo/paclitaxel − 12.7 months; p = 0.535; NS | [51s] |
Bev: Bevacizumab; Carbo: Carboplatin; Cis: Cisplatin; Gem: Gemcitabine; NS: No statistically significant difference: NSCLC: Non-small-cell lung cancer: OS: Overall survival: p.o.: Perorem: Pern: Pemetrexed: PFS: Progression-free survival: S: Statistically significant difference:.