Table 1.
Overview of Outcome of Clinical Trials Using EGFR-Targeted Therapy in Malignant Gliomas
| Agent | Targets | Phase | Study Design | Outcomes | References |
|---|---|---|---|---|---|
|
Small Molecules Gefitinib (Iressa) |
EGFR | II | single agent 53 recurrent GBM |
6-month EFS: 13% median OS: 39.4 wks median EFS: 8.1 wks No correlation between EGFR and OS or EFS |
Rich 2004 [49] |
| II | single agent 28 GBM, AO & AA |
6-month PFS: 14.3% median OS: 24.6 wks No correlation between EGFR/p-Akt and response |
Franceschi 2007 [50] | ||
| I | gefitinib+sirolimus 34 recurrent GBM & AA |
6-month PFS: 23.5% median PFS: 27.4 wks PR: 14%, SD: 38% |
Reardon 2006 [51] | ||
| I/II | gefitinib+everolimus 22 GBM |
6-month PFS, 4.5% median PFS: 2.6 months median OS: 5.8 months PR: 14%, SD: 38% No correlation between EGFR/PTEN and response |
Kriesl 2009 [52] | ||
| I | gefitinib+TMZ 26 GBM |
Recommendations for phase-2 doses | Prados 2008 [53] | ||
| I | radiosurgery 15 recurrent GBM & AA |
6-month PFS: 63% median PFS: 7 months median OS: 29 months (all pt’s) median OS: 21 months (GBM) |
Schwer 2008 [54] | ||
| Erlotinib (Tarceva) |
EGFR | II | single agent 67 recurrent GBM & AA |
median PFS: 12 wks (GBM) median PFS: 8.6 wks (AA) limited activity as single agent |
Raizer 20041 |
| II | single agent 58 recurrent GBM |
6-month PFS: 17% median OS: 10 months No correlation between EGFR and response |
Cloughesy 20052 | ||
| II | erlotinib+sirolimus 32 recurrent GBM |
6-month PFS: 3.1% negligible activity p-AKT, but not EGFR/EGFRvIII/PTEN correlates with response. |
Reardon 2009 [55] | ||
| I | Arm 1: erlotinib alone Arm 2: erlotinib+TMZ 83 GBM |
Recommendations for phase-2 doses | Prados 2006 [57] | ||
| I/II | erlotinib+TMZ+RT 97 newly diagnosed GBM |
median OS: 15.3 months biomarkers: pt’s not sensitive to er lotinib No correlation between EGFR/EGFRvIII/ PTEN and response |
Brown 2008 [58] | ||
| II | Arm 1: erlotinib alone Arm 2: TMZ or BCNU 110 recurrent GBM |
6-month PFS: 11.4% (Arm 1) 6-month PFS: 24% (Arm 2) Limited activity of erlotinib No correlation between EGFR/EGFRvIII PTEN/p-Akt and response to erlotinib |
Van den Bent 2009 [59] | ||
| II | erlotinib+carboplatin 43 recurrent GBM |
6-month PSF: 14% median PSF: 9 wks median PS: 30 wks No correlation between EGFR/PTEN/ Akt and PFS or OS |
de Groot 2008 [60] | ||
| I | erlotiniib+RT 19 GBM |
median OS: 55 wks | Krishnan 2006 [61] | ||
| II | erlotinib+ bevacizumab 56 recurrent GBM & AA |
6-month PFS: 25% (GBM) 6-month PFS: 50% (AA) Full results to be reported |
Sathornsumetee 20093 | ||
| Lapatinib (Tykerb/Tyverb) |
EGFR/HER2 | I/II | single agent 7 recurrent GBM (I) 17 recurrent GBM (II) |
No significant lapatinib activity No correlation between EG FRvIII/PTEN and response |
Thiessen 2009 [63] |
|
Antibodies Cetuximab (Erbitux) |
EGFR | I/II | cetuximab+RT+TMZ 17 GBM |
6-month PFS: 81% 12-month PFS: 37% 12-month OS: 87% |
Combs 20094 |
| II | single agent Arm 1: 28 GBM with EGFR amplification Arm 2: 27 GBM with no EGFR amplification |
No significant cetuximab activity No correlation between EGFR and response |
Neyns 2009 [64] | ||
| II | cetuximab+ bevacizumab+ irinotecan 32 recurrent GBM |
Response rates similar to bevacizu mab+irinotecan |
Lassen 20085 |
EFS: event-free survival, OS: overall survival, PFS: progression-free survival, PR: partial response, SD: stable disease.
AA: anaplastic astrocytoma, AO: anaplastic oligodendrogliomas, RT: radiation therapy.