A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients

Survival for glioblastoma (GBM) patients with an unmethyated MGMT promoter in their tumor is generally worse than methylated MGMT tumors, as temozolomide (TMZ) response is limited. How to better treat patients with unmethylated MGMT is unknown. We performed a trial combining erlotinib and bevacizuma...

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Veröffentlicht in:Journal of neuro-oncology 2016-01, Vol.126 (1), p.185-192
Hauptverfasser: Raizer, J. J., Giglio, P., Hu, J., Groves, M., Merrell, R., Conrad, C., Phuphanich, S., Puduvalli, V. K., Loghin, M., Paleologos, N., Yuan, Y., Liu, D., Rademaker, A., Yung, W. K., Vaillant, B., Rudnick, J., Chamberlain, M., Vick, N., Grimm, S., Tremont-Lukats, I. W., De Groot, J., Aldape, K., Gilbert, M. R.
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container_end_page 192
container_issue 1
container_start_page 185
container_title Journal of neuro-oncology
container_volume 126
creator Raizer, J. J.
Giglio, P.
Hu, J.
Groves, M.
Merrell, R.
Conrad, C.
Phuphanich, S.
Puduvalli, V. K.
Loghin, M.
Paleologos, N.
Yuan, Y.
Liu, D.
Rademaker, A.
Yung, W. K.
Vaillant, B.
Rudnick, J.
Chamberlain, M.
Vick, N.
Grimm, S.
Tremont-Lukats, I. W.
De Groot, J.
Aldape, K.
Gilbert, M. R.
description Survival for glioblastoma (GBM) patients with an unmethyated MGMT promoter in their tumor is generally worse than methylated MGMT tumors, as temozolomide (TMZ) response is limited. How to better treat patients with unmethylated MGMT is unknown. We performed a trial combining erlotinib and bevacizumab in unmethylated GBM patients after completion of radiation (RT) and TMZ. GBM patients with an unmethylated MGMT promoter were trial eligible. Patient received standard RT (60 Gy) and TMZ (75 mg/m 2  × 6 weeks) after surgical resection of their tumor. After completion of RT they started erlotinib 150 mg daily and bevacizumab 10 mg/kg every 2 weeks until progression. Imaging evaluations occurred every 8 weeks. The primary endpoint was overall survival. Of the 48 unmethylated patients enrolled, 46 were evaluable (29 men and 17 women); median age was 55.5 years (29–75) and median KPS was 90 (70–100). All patients completed RT with TMZ. The median number of cycles (1 cycle was 4 weeks) was 8 (2–47). Forty-one patients either progressed or died with a median progression free survival of 9.2 months. At a follow up of 33 months the median overall survival was 13.2 months. There were no unexpected toxicities and most observed toxicities were categorized as CTC grade 1 or 2. The combination of erlotinib and bevacizumab is tolerable but did not meet our primary endpoint of increasing survival. Importantly, more trials are needed to find better therapies for GBM patients with an unmethylated MGMT promoter.
doi_str_mv 10.1007/s11060-015-1958-z
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J. ; Giglio, P. ; Hu, J. ; Groves, M. ; Merrell, R. ; Conrad, C. ; Phuphanich, S. ; Puduvalli, V. K. ; Loghin, M. ; Paleologos, N. ; Yuan, Y. ; Liu, D. ; Rademaker, A. ; Yung, W. K. ; Vaillant, B. ; Rudnick, J. ; Chamberlain, M. ; Vick, N. ; Grimm, S. ; Tremont-Lukats, I. W. ; De Groot, J. ; Aldape, K. ; Gilbert, M. R.</creator><creatorcontrib>Raizer, J. J. ; Giglio, P. ; Hu, J. ; Groves, M. ; Merrell, R. ; Conrad, C. ; Phuphanich, S. ; Puduvalli, V. K. ; Loghin, M. ; Paleologos, N. ; Yuan, Y. ; Liu, D. ; Rademaker, A. ; Yung, W. K. ; Vaillant, B. ; Rudnick, J. ; Chamberlain, M. ; Vick, N. ; Grimm, S. ; Tremont-Lukats, I. W. ; De Groot, J. ; Aldape, K. ; Gilbert, M. R. ; Brain Tumor Trials Collaborative ; Brain Tumor Trials Collaborative</creatorcontrib><description>Survival for glioblastoma (GBM) patients with an unmethyated MGMT promoter in their tumor is generally worse than methylated MGMT tumors, as temozolomide (TMZ) response is limited. 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subjects Adult
Antineoplastic Agents - therapeutic use
Bevacizumab - therapeutic use
Brain Neoplasms - drug therapy
Clinical Study
Dacarbazine - adverse effects
Dacarbazine - analogs & derivatives
Disease-Free Survival
DNA Methylation
DNA Modification Methylases - genetics
Erlotinib Hydrochloride - therapeutic use
Female
Glioblastoma - drug therapy
Humans
Male
Medicine
Medicine & Public Health
Middle Aged
Neurology
Oncology
Prognosis
Radiotherapy - adverse effects
Temozolomide
Treatment Outcome
Young Adult
title A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients
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