Table 2.
Results of analyzed studies with objectifiable baseline characteristics.
| Publication | Study Type | Recruitment Interval | pGBM Cohort (n) | Age at Study Entry ° (Years) (Median/Range) |
Disease Status | Intervention | Primary Outcome GBM Cohort (EFS; PFS; OS) | Secondary Outcome (Toxicity; Toleration of Treatment) |
Therapeutic Effect | Quality Assessment NOS/RoB-2 (points) |
|---|---|---|---|---|---|---|---|---|---|---|
| Gururangan et al., 2010 [51] |
prospective phase-Ⅱ cohort trial | 10/2006–09/2008 | 8 | 15.7 (5.6–20.1) |
r/r | BEV plus irinotecan | 2/8 SD at >12 weeks, of these 2 patients, median PFS: 8.3 months no sustained OR | 20% toxicity with interruption of treatment | no efficacy in recurrent pGBM | 5 (fair) |
| MacDonald et al., 2013 [50] |
prospective phase-Ⅱ cohort trial | 06/2008–12/2010 | 18 | 14.2 (1.1–20.3) |
r/r | cilengitide | 1/18 SD at 19 months | low toxicity rate, well tolerated | no efficacy in recurrent pGBM | 5 (fair) |
| Robinson et al., 2014 [52] |
multicenter, prospective phase-Ⅱ cohort trial | 01/2005–03/2009 | 9 | 10 (0.6–21) |
r/r | metronomic oral celecoxib, thalidomide, fenofibrate, low dose CPM and etoposide | 1/9 SD at 27 weeks | low toxicity rate, well tolerated | no efficacy in recurrent pGBM | 5 (fair) |
| Wetmore et al., 2016 [54] |
multicenter, prospec-tive phase-Ⅱ cohort trial | 01/2012–06/2013 | 7 | 14.5 (4.7–19.9) |
r/r | sunitinib | Response rate (=CR or PR for at least 8 weeks): 0% | low toxicity rate, well tolerated | closing at interim analysis due to lack of efficiacy | 6 (good) |
| Grill et al., HERBY trial 2018 [48] |
randomized controlled trial | 10/2011–02/2015 | 84 | 11 (3–17) |
newly diagnosed | BEV | HR: 1.37 (95% CI 0.83 to 2.27) for RT plus TMZ compared to RT + TMZ + BEV | no safety concerns; more AEs in BEV-cohort | No measurable effect for unmethylated pGBM | some concerns (RoB-2) |
| Meng-Fen Su et al., 2020 [53] |
multicenter, prospective phase-Ⅱ cohort trial | 09/2009–08/2015 | 11 | 7.9 (3.2–19.9) |
newly diagnosed | VPA and radiation followed by VPA and BEV | median EFS: 10.5 months median OS: 14.9 months |
2 treatment interruptions after addition of BEV; RT and VPA with good tolerance | no improvement of OS | 5 (fair) |
° of the whole HGG cohort; pGBM = pediatric glioblastoma, NOS = Newcastle-Ottawa scale, RoB2 = Risk of Bias 2 tool, r/r = relapsed/refractory disease, PFS = progression free survival, EFS = event free survival, OS = overall survival, OR = objective response, CR = complete remission, PR = partial remission, HR = hazard ratio, CI = confidence interval, RT = radiotherapy, TMZ = temozolomide, BEV = bevacizumab, AEs = adverse events, VPA = valproic acid, CPM = cyclophosphamide.