Table 1.
Overview of the filtered trials’ study design, efficacy endpoints, and prognostic patient characteristics in the target population including adult patients aged 18 years and above (younger cohort)1,4,6,13,15–17,19,22–24,26
| NCTID (primary completion date) | First author, year, journal | Eligibility criteria | Treatment arms Arm 1: control Arm 2: intervention |
Blind | # Pat | Gender m (%) | Age in years | MGMT-prom meth (%) | IDH-mut (%) | Extent of resection (%) | mOS HR (P-value) |
mPFS HR (P-value) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EORTC/NCIC NCT00006353 (2002–03) |
Stupp 2005 NEJM, Stupp 2009 |
ndGBM, 18–70 years, WHO PS 0-2 | Arm 1:RT Arm 2: RT+TMZ (Stupp) |
No | 573 | Arm 1: 61% Arm 2: 64% |
Arm 1: 57 (23–71) Arm 2: 56 (19–70) |
Arm 1: +MGMT: 46% −MGMT: 54% Arm 2: +MGMT: 43.4% −MGMT: 56.6% |
NA | Arm 1: Biopsy: 16%, Partial: 45% Complete: 40% Arm 2: Biopsy: 17%, Partial: 44% Complete: 39% |
Arm 1: 12.1 mo [−MGMT: 11.8 mo; +MGMT: 15.3 mo] Arm 2: 14.6 mo [−MGMT: 12.6 mo; +MGMT: 23.4 mo] HR 0.63 (P < .001) |
Arm 1: 5.0 mo Arm 2: 6.9 mo HR 0.54 (P < .001) |
| EF-14 NCT00916409 (2016–12) |
Stupp 2017 JAMA |
ndGBM, supratentorial, ≥18 years, KPS ≥70 | Arm 1: adjuvant TMZ (Stupp) Arm 2: adjuvant TMZ (Stupp) + TTFields |
No | 695 | Arm 1: 69% Arm 2: 68% |
Arm 1: 57 (19–80) Arm 2: 56 (19–83) |
Arm 1: +MGMT: 42% −MGMT: 51% Arm 2: +MGMT: 36% −MGMT: 54% |
IDH1-R132H: Arm 1: tested 52%, mut 5%, negative 95% Arm 2: tested 56%, mut 7%, negative 92% |
Arm 1: Biopsy: 13%, Partial: 33% GTR: 54% Arm 2: Biopsy: 13%, Partial: 34% GTR: 53% |
Arm 1: 16.0 mo [−MGMT:14.7 mo, +MGMT: 21.2 mo] Arm 2: 20.9 mo [−MGMT: 16.9 mo, +MGMT: 31.6 mo] HR 0.63 (P < .001) −MGMT: HR 0.66, +MGMT: HR 0.62 |
Arm 1: 4.0 mo Arm 2: 6.7 mo HR 0.63 (P < .001) |
| CeTeG NCT01149109 (2017–04) |
Herrlinger 2019 Lancet | ndGBM/gliosarcoma, +MGMT, 18–70 years, KPS ≥70 | Arm 1: RT+TMZ (Stupp) Arm 2: RT+TMZ+CCNU |
No | 141 | Arm 1: 48% Arm 2: 71% |
Arm 1: 56 (28–70) Arm 2: 59 (31–71) |
+MGMT: 100% | IDH1/2: total: mut 6%, wt 80%, oligo 5%; Arm 1: mut 8%, wt 83%, oligo 5%; Arm 2: mut 5%, wt 77%, oligo 5% |
Arm 1: Biopsy: 2%, Partial: 35% Complete: 63% Arm 2: Biopsy: 5%, Partial: 36% Complete: 59% |
Arm 1: mITT 31.4 mo; ITT 30.4 mo, PPP 30.4 mo Arm 2: mITT 48.1 mo; ITT 46.9 mo, PPP 40.3 mo HR 0.60 (P = .0492) |
Arm 1: 16.7 mo Arm 2: 16.7 mo HR 0.91 (P = .6775) |
| ASPECT EudraCT 2004-000464-28 | Westphal M 2013 Lancet Oncology | ndGBM, completely resectable, unifocal, supratentorial, KPS ≥70, 18–70 years | Arm 1: Standard care Arm 2: Standard care + sitimagene ceradenovec |
No | 250 | Arm 1: 65% Arm 2: 59% |
Arm 1: 57.0 (26–70) Arm 2: 58.0 (20–70) |
Arm 1: +MGMT: 24%, −MGMT: 76% Arm 2: +MGMT: 35%, −MGMT: 65% |
NA | Arm 1: radical: 81%, partial: 19% Arm 2: radical: 83%, partial: 17% |
Arm 1: 452 days Arm 2: 497 days HR 1.18 (P = .31) |
Not available |
|
NCT00304031 (2011–02) |
Gilbert MR 2013 JCO | ndGBM, ≥18 years, KPS ≥60 | Arm 1: RT+TMZ (Stupp 6–12 m) Arm 2: RT+TMZ (dose dense 6–12 m) |
No | 833 | Arm 1: 58% Arm 2: 56% |
Arm 1: <50: 27%, ≥50: 73% Arm 2: <50:26%, ≥50: 74% |
Arm 1: +MGMT: 30%, −MGMT: 62% Arm 2: +MGMT: 29%, −MGMT: 62% |
NA | Arm 1: biopsy 3%, Partial 41%, Total: 56%; Arm 2: biopsy 3%, Partial: 45%, Total: 52% |
Arm 1: 16.6 mo [−MGMT: 14.6 mo, +MGMT: 21.4 mo] Arm 2: 14.9 mo [−MGMT: 13.3 mo, +MGMT: 20.2 mo] HR 1.03 (P = .63) −MGMT: HR 0.99 (P = .44) +MGMT: HR 1.19 (P = .86) |
Arm 1: 5.5 mo; −MGMT: 5.1 mo, +MGMT: 6.5 mo Arm 2: 6.7 mo; −MGMT: 6.0 mo, +MGMT:10.1 mo HR 0.87 (P = .06); −MGMT: HR 0.88 (P = .15), +MGMT:HR 0.87 (P = .33) |
|
NCT00807027 (2012–10) |
Kong DS 2017 Oncotarget | ndGBM, 18–70 years, KPS ≥60 | Arm 1: RT+TMZ (Stupp) Arm 2: RT+TMZ (Stupp)+(CIK) cell immunotherapy |
No | 180 | Arm 1: 57.3% Arm 2: 56.0% |
Arm 1: 54 (23–68) Arm 2: 55 (19–69) |
NA | NA | Arm 1: biopsy 11.2%, Partial: 6.7%, Subtotal: 28.1%, Gross Total: 53.9% Arm 2: biopsy 13.2%; Partial: 8.8%, Subtotal: 29.7%, Gross Total: 48.4% |
Arm 1: 16.88 mo Arm 2: 22.47 mo HR 0.693 (P = .5237) |
Arm 1: 5.4 mo Arm 2: 8.1 mo HR 0.745 (P = .0401) |
| CENTRIC NCT00689221 (2012–11) |
Stupp R 2014 Lancet Oncol | ndGBM, supratentorial, ≥18 years, +MGMT, ECOG PS 0–1 | Arm 1: RT+TMZ (Stupp) Arm 2: RT+TMZ (Stupp)+cilengitide |
No | 545 | Arm 1: 52% Arm 2: 54% |
Arm 1: 58 (22–79) Arm 2: 58 (22–81) |
+MGMT: 100% | NA | Arm 1: biopsy 3%, Partial: 47%, Gross Total: 50% Arm 2: biopsy 3%, Partial: 48%, Gross Total: 49% |
Arm 1: 26.3 mo Arm 2: 26.3 mo HR 1.02 (P = .86) |
Arm 1: 10.7 mo Arm 2: 13.5 mo HR 0.93 (P = .46) |
| AVAglio NCT00943826 (2013–02) |
Chinot OL 2014 NEJM | ndGBM, supratentorial, ≥18 years, WHO PS 0–2 | Arm 1: RT+TMZ (Stupp)+placebo (concomitant) Arm 2: RT+TMZ (Stupp)+bevacizumab (concomitant) |
Double | 921 | Arm 1: 64.4% Arm 2: 61.6% |
Arm 1: 56 (18-79) Arm 2: 57 (20–84) |
Arm 1: +MGMT: 25.9%, −MGMT: 51.0% Arm 2: +MGMT: 25.5%, −MGMT: 49.1% |
NA | Arm 1: biopsy 9.5%, Partial: 48.2%, Complete: 42.3% Arm 2: biopsy 13.1%, Partial: 45.9%, Complete: 41.0 |
Arm 1: 16.7 mo Arm 2: 16.8 mo HR 0.88 (P = .10) |
Arm 1: 6.2 mo Arm 2: 10.6 mo HR 0.64 (P < .001) |
| RTOG 0825 NCT00884741 (2013–03) |
Gilbert MR 2014 NEJM | ndGBM, ≥18 years, KPS ≥70 |
Arm 1: RT+TMZ (Stupp 6–12 m) + placebo (adjuvant) Arm 2: RT+TMZ (Stupp 6–12 m)+bevacizumab (adjuvant) |
Double | 637 | Arm 1: 63% Arm 2: 57% |
Arm 1: <50: 21%, ≥50:79% Arm 2: <50: 18%, ≥50: 82% |
Arm 1: +MGMT: 28%, −MGMT: 69% Arm 2: +MGMT: 29%, −MGMT: 69% |
NA | Arm 1: Partial: 38%, Total: 59%, other: 3% Arm 2: Partial: 34%, Total: 63%, other: 3% |
Arm 1: 16.1 mo Arm 2: 15.7 mo HR 1.13 (P = .21) |
Arm 1: 7.3 mo Arm 2: 10.7 mo HR 0.79 (P = .007) |
| ACT IV NCT01480479 (2016–11) |
Weller M 2017 Lancet Oncology | ndGBM, +EGFRvIII, maximal resected, supratentorial, ECOG PS 0–2, ≥18 years | Arm 1: RT+TMZ (Stupp ≥6 m)+placebo Arm 2: RT+TMZ (Stupp ≥6 m)+Rindopepimut |
Double | 745 (MRD 405) | Arm 1: 58% Arm 2: 68% |
Arm 1: 57 (51–64) Arm 2: 59 (51–64) |
Arm 1: +MGMT: 35%, −MGMT: 57% Arm 2: +MGMT: 35%, −MGMT: 55% |
NA | Maximal resection for eligibility | Arm 1: MRD 20.0 mo; ITT 17.4 Arm 2: MRD 20.1 mo; ITT 17.4 MRD HR 1.01 (P = .93) ITT: HR 0.89 (P = .22) |
Arm 1: MRD 7.4 mo; ITT 5.6 Arm 2: MRD 8.0 mo; ITT 7.1 MRD HR 1.01 (P = .91) ITT: HR 0.94 (P = .51) |
| OSAG 101—BSA-05 NCT00753246, EudraCT 2005–003101-85 | Westphal M 2015 EJC | ndGBM, 18–70 years, KPS ≥70 | Arm 1: RT+TMZ (Stupp) Arm 2: RT+TMZ (Stupp) + nimotuzumab |
No | 149 | Arm 1: 63.4% Arm 2: 59.2% |
Arm 1: 56 (30–70) Arm 2: 55 (25–71) |
Arm 1: +MGMT: 22.5%, −MGMT: 45.1% Arm 2: +MGMT: 21.1%, −MGMT: 46.5% |
NA | Arm 1: residual tumor: 57.7%; no residual tumor: 42.3% Arm 2: residual tumor: 56.3% no residual tumor: 43.7%; |
Arm 1: 19.6 mo [−MGMT 15.5 mo, +MGMT: 33.8 mo] Arm 2: 22.3 mo [−MGMT 19.5 mo, +MGMT: nr] HR 0.86 (P = .49) [−MGMT HR 0.81 (P = .46), +MGMT: HR 0.86 (P = .80)] |
Arm 1: 5.8 mo; −MGMT: 5.8 mo, +MGMT: 12.7 mo, Arm 2: 7.7 mo; −MGMT: 8.3 mo, +MGMT: 8.9 mo HR 0.95 (P = .79) |
ECOG PS, ECOG Performance Score; HR, hazard ratio; ITT, intention-to-treat population; KPS, Karnofsky Performance Score; +MGMT, methylated MGMT promoter; −MGMT, unmethylated MGMT promoter; mITT, modified intention-to-treat population; mo, months; mut, mutated; NA, not available; nr, not reached; ppp, per protocol population; RT, radiotherapy; TMZ, temozolomide; WHO PS, WHO Performance Score; wt, wildtype. Green font marks significant results (P <.05), red font marks non significant results (P ≥.05). Positive studies are provided in blue.