Table 1.
Critical clinical trials investigating anti-angiogenic therapy in glioblastoma.
| Author (year) | Trial | Phase | Disease | Regimen | Patient number | Median PFS (m) | Median OS (m) | Notes |
|---|---|---|---|---|---|---|---|---|
| Friedman et al. (2009) | BRAIN | II | rGBM | BEV | 85 | 4.2 | 9.2 | The first large prospective study demonstrating that BEV ± irinotecan is well tolerated and achieves certain therapeutic effects in rGBM. |
| BEV + irinotecan | 82 | 5.6 | 8.7 | |||||
| Kreisl et al. (2009) | NCI | II | rGBM | BEV | 48 | 4.0 | 7.8 | A study shows that single-agent BEV is well tolerated and has biological activity in rGBM. Data reveals that imaging biomarkers can be applied to monitor and predict treatment responses. |
| Taal et al. (2014) | BELOB | II | rGBM | BEV | 50 | 3 | 8 | A study shows promising effects of BEV + lomustine in rGBM patients. The results in the BEV + lomustine group now serve as the ‘comparison standard’ for the investigations focusing on rGBM. |
| Lomustine | 46 | 2 | 8 | |||||
| BEV + lomustine | 44 | 11 | 11 | |||||
| Wick et al. (2017) | EORTC 26101 | III | rGBM | BEV + lomustine | 288 | 4.2 | 9.1 | PFS was significantly prolonged in the BEV + lomustine group, but an OS advantage was not conferred. More adverse events were observed in the BEV + lomustine group due to the longer duration of treatment. |
| Lomustine | 149 | 1.5 | 8.6 | |||||
| Chinot et al. (2014) | AVAglio | III | nGBM | BEV + TMZ/RT | 458 | 10.6 | 16.9 | The study observed a significant improvement in PFS (P < 0.0001) but not in OS. Although the maintenance of the performance status is observed in the BEV + TMZ/RT group, a higher incidence of adverse events is also documented. |
| TMZ/RT | 463 | 6.2 | 16.8 | |||||
| Gilbert et al. (2014) | RTOG 0825 | III | nGBM | BEV + TMZ/RT | 312 | 10.7 | 15.7 | Although there is a similar increase in PFS (P < 0.01) and not in OS, a more frequent increased symptom burden and declined neurocognitive function is noticed in the BEV + TMZ/RT group. |
| TMZ/RT | 309 | 7.3 | 16.1 | |||||
| Batchelor et al. (2013b) | REGAL | III | rGBM | Cediranib | 131 | 3.1 | 8.0 | This study fails to demonstrate a benefit in PFS and OS for cediranib±irinotecan versus lomustine alone in patients with rGBM. Patients in the cediranib+lomustine arm experienced higher rates of toxicities than patients in both monotherapy arms. |
| Cediranib + lomustine | 129 | 4.2 | 9.4 | |||||
| Lomustine | 65 | 2.7 | 9.8 |
Abbreviations: rGBM, recurrent glioblastoma; nGBM, newly diagnosed glioblastoma; BEV, bevacizumab; TMZ, temozolomide; RT, radiotherapy; PFS, progression-free survival; OS, overall survival.