Table 1. Selected studies evaluating angiogenesis inhibitors in advanced colorectal cancer.
| Study | Treatment arms | Number of patients | Response rates (%) | P-value | Median progression-free survival (months) | P-value | Median overall survival (months) | P-value |
|---|---|---|---|---|---|---|---|---|
| First line | ||||||||
| Kabbinavar et al (2003) | 5-FU/LV | 36 | 17 | — | 5.2 | — | 13.8 | NR |
| 5-FU/LV/BEV (5 mgkg−1) | 35 | 40 | 0.029 | 9.0 | 0.005 | 21.5 | NR | |
| 5-FU/LV/BEV (10 mgkg−1) | 33 | 24 | 0.434 | 7.2 | 0.217 | 16.1 | NR | |
| Hurwitz et al (2004) | IFL | 411 | 34.8 | — | 6.2 | — | 15.6 | — |
| AVF 2107 | IFL/BEV | 402 | 44.8 | 0.004 | 10.6 | <0.001 | 20.3 | <0.001 |
| 5-FU/LV/BEV | 110 | 40.0 | 0.66 | 8.8 | 0.4192 | 18.3 | 0.2521 | |
| Kabbinavar et al (2005b) | 5-FU/LV | 105 | 15.2 | — | 5.5 | — | 12.9 | — |
| 5-FU/LV/BEV | 104 | 26.0 | 0.055 | 9.2 | 0.0002 | 16.6 | 0.16 | |
| Kabbinavar et al (2005a) | 5-FU/LV or IFL | 241 | 24.5 | — | 5.55 | - | 14.6 | — |
| 5-FU/LV/BEV | 249 | 34.1 | 0.019 | 8.77 | 0.0001 | 17.9 | 0.0081 | |
| Saltz et al (2008) | FOLFOX or CAPOX | 701 | 38 | — | 8.0 | 0.0023 | 19.9 | 0.077 |
| XELOX-1/ NO16966 | FOLFOX/CAPOX + BEV | 699 | 38 | 0.99 | 9.4 | 21.3 | ||
| Tol et al (2009) | CAPOX + BEV | 368 | 50 | — | 10.7 | — | 20.3 | — |
| CAIRO 2 | CAPOX + BEV + cetuximab | 368 | 52.7 | 0.49 | 9.4 | 0.01 | 19.4 | 0.16 |
| Hecht et al (2009) | FOLFOX + BEV | 410 | 48 | — | 11.4 | HR: 1.27 | 24.5 | HR: 1.43 |
| PACCE | FOLFOX + BEV + PAN | 413 | 46 | NS | 10.0 | (95% CI: 1.06–1.52) | 19.4 | (95% CI: 1.11–1.83) |
| Hecht et al (2009) | FOLFIRI + BEV | 115 | 40 | — | 11.7 | HR: 1.19 | 20.5 | HR: 1.42 |
| PACCE | FOLFIRI + BEV + PAN | 115 | 43 | NS | 10.1 | (95% CI: 0.79–1.79 | 20.7 | (95% CI: 0.77–2.62) |
| Reinacher-Schick et al (2008) a | CAPOX + BEV | 127 | 53 | — | 10.4 | — | 26.7 | — |
| AIO 0604 | CAPIRI + BEV | 120 | 55 | NR | 12.1 | 0.27 | Not reached | 0.55 |
| Hecht et al (2009) | FOLFOX | 583 | 46 | — | 7.7 | — | 20.5 | — |
| CONFIRM 1 | FOLFOX + PTK/ZK | 585 | 42 | NS | 9.1 | 0.108 | 21.4 | 0.260 |
| Grothey et al (2008b) BriTEb | Chemotherapy + BEV (non-randomised US cohort study) | 1953 | NR | NR | 9.9 | NR | 25.1 | NR |
| Berry et al (2008) (BEATb) | Chemotherapy + BEV (non-randomised non-US cohort study) | 1914 | NR | NR | 10.8 | NR | 22.7 | NR |
| Second line | ||||||||
| Giantonio et al (2007) | FOLFOX | 291 | 8.6 | — | 4.7 | — | 10.8 | — |
| ECOG E3200 | FOLFOX/BEV (10 mg kg−1) | 289 | 22.7 | <0.0001 | 7.3 | <0.0001 | 12.9 | 0.0011 |
| BEV (10 mg kg−1) | 243 | 3.3 | 2.7 | 10.2 | ||||
| Kohne et al (2007) | FOLFOX | 429 | 18 | — | 4.1 | — | 11.8 | — |
| CONFIRM 2 | FOLFOX + PTK/ZK | 426 | 19 | NS | 5.6 | 0.026 | 12.1 | 0.511 |
| Cunningham et al (2008) a | A. FOLFOX+BEV | 66 | 27 | 7.8 | B vs A | NR | — | |
| HORIZON I | B. FOLFOX+cediranib (low dose) | 71 | 18 | — | 5.8 | 0.29 | NR | |
| C. FOLFOX+cediranib (high dose) | 73 | 19 | NR | 7.2 | C vs A 0.79 | NR | NS | |
| Saltz et al (2007) a | Irinotecan/cetuximab/ BEV | 43 | 37 | — | 7.3 | — | 14.5 | — |
| BOND 2 | Cetuximab/ BEV | 40 | 20 | NR | 4.9 | NR | 11.4 | NR |
LV=leucovorin; FOLFOX: oxaliplatin/infused 5-FU/LV; BEV=bevacizumab; CAPOX: capecitabine/oxaliplatin; IFL=irinotecan/bolus 5-FU/LV; FOLFIRI: irinotecan-infused 5-FU/LV; CAPIRI: capecitabine/irinotecan; PAN=panitumumab; NR=not reported; NS=Not significant; HR=hazard ratio; CI=confidence interval.
The first treatment arm of each study was the control arm. Unless stated, all bevacixumab was given at 2.5 mg kg−1 per week. All P-values were compared with control arms.
a
Randomised phase II studies.
b
Observational registry studies.