Table 1.
Pivotal anti-VEGF phase III clinical trials (acronyms are elaborated below table)
| Anti-VEGF drug | Indication | Phase III Trials | Results (control vs. anti-VEGF drug/combination) | Status of trial/drug | |||
|---|---|---|---|---|---|---|---|
| median overall survival (OS) |
progression- free survival (PFS) |
duration of response (DR) |
objective response (OR) |
√ = completed;√√ FDA- approved; X= on-going |
|||
| Monoclonal Antibody | (months) | (months) | (months) | % | |||
| IFL −/+ bevacizumab | first-line MCC | AV2107g Hurwitz et al., ’04 | 15.6 vs. 20.3 | 6.2 vs. 10.6 | 7.1 vs. 10.4 | 34.8 vs. 44.8 | √, √√, improved OS, PFS, DR, OR |
| FOLFOX4 −/+ bevacizumab | 2nd-line MCC | ECOG 3200 Giantonio et al., ’05 | 10.8 vs. 12.9 | 4.8 vs. 7.2 | 9.2 vs. 21.8 | √, √√, improved OS, avastin-only arm discont’d | |
| paclitaxel & carboplatin −/+ bevacizumab | first-line NSCLC | ECOG 4599 Sandler et al., ’06 | 10.3 vs. 12.3 | 4.5 vs. 6.2 | 15 vs. 35 | √, √√, improved OS, PFS, OR | |
| paclitaxel −/+ bevacizumab | first-line MBC | ECOG 2100 Miller et al., ’05b | 25.2 vs. 28.4 p=0.1 | 6.11 vs. 11.4 | 13.8 vs. 29.9 | X, FDA review, improved PFS, OR; OS data immature | |
| Small molecule antagonists | |||||||
| placebo vs. sorafenib | 2nd-line mRCC | TARGETs Escudier et al., ’07 | 15.9 vs. 19.3*(*48% crossover) | 2.8 vs. 5.5* | 0, 2, 53 vs. <1, 10, 74* * complete/partial-response, stable disease | X, √√, improved PFS study unblinded | |
| IFN-alfa vs. sunitinib malate | first-line mRCC | NCT000-98657/-83889 Motzer et al., ’07 | median survival data not mature | 5 vs. 11 | 6 vs. 31 | X, √√, study unblinded, improved PFS & OR; OS data pending | |
| placebo vs. sunitinib malate | imatinib-resistant GIST | NCT00075218 Demetri et al. ’06 | 56.9% vs. 79.4%**6 month survival ASCO ’06 | 1.6 vs. 6.8 | 0 & 48 vs. 7 & 58* *partial response, stable disease, >22wk | √, √√, improved PFS, OS; study unblinded | |
| Humanized anti-VEGF Fab fragment | Loss of visual acuity % who lost <15 letters | Severe vision loss %who lost ≥30 letters | % Legally blind ≤20/200 | Gain in visual acuity (% of subjects) gain of ≥ 15 letters | |||
| 0.3&0.5mg ranibizumab (Rz) vs. sham injection | wet AMD | MARINA trial RosenfeldRosenfeld et al., ’06 | 1 year: 95 & 95 vs. 62% 2 years: 92 & 90 vs. 53% |
0.8 & 1.2 vs. 14.3% 3.4 & 2.5 vs. 22.7% |
12.2 &11.7 vs 43 14.7 &15 vs 47.9 |
√, √√ improved visual acuity | |
| 0.3 & 0.5mg Rz + sham PDT vs. sham ocular injections + PDT | wet AMD | ANCHOR trial Brown et al., ’06 | 94 & 96 vs. 64% | 0 & 0 vs. 13.3% | 22.1 & 16.4% vs. 60.1% | 35.7 & 40.3% vs. 5.6 % | √, 2-year data reported at Retina ’07; study extended as HORIZON |
| Pegylated oligonucleotide aptamer | |||||||
| 0.3, 1, & 3mg pegaptanib sodium vs. sham | wet AMD | VISION trials Gragoudas et al.,’04 (Chakravarthy et al., ’06)* |
70, 71, & 65 vs. 55% 0.3, 1, 3mg vs sham, 13.5mo (59 vs. 45%)* (0.3mg & 25.5 months)* |
10, 8 & 14 vs. 22% (13.5 months) | 38, 43 & 44% vs. 56% (13.5 months) | 6, 7, 4 vs. 2% (13.5 months) | √, √√ improved visual acuity |
irinotecan/5-FU/leucovorin (IFL); oxaliplatin/5-FU/leucovorin (FOLFOX4); verteporfin photodynamic therapy (PDT); metastatic colorectal cancer (MCC); non-squamous, non-small cell lung cancer (NSCLC); metastatic breast cancer (MBC); metastatic renal cell carcinoma (mRCC); gastrointestinal stromal tumors (GIST); neovascular age-related macular degeneration (wet AMD)