title: A phase II study of bevacizumab and erlotinib after radiation  and temozolomide in MGMT unmethylated GBM patients.
abstract: 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/m2 × 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.
authors.affiliation: Department of Neurology, Northwestern University, 710 North Lake Shore Drive, Abbott Hall, Room 1123, Chicago, IL, 60611, USA. jraizer@nm.org.
authors.forename: J J
authors.initials: JJ
authors.lastname: Raizer
authors.affiliation: James Cancer Hospital, Ohio State University, Columbus, OH, USA.
authors.forename: P
authors.initials: P
authors.lastname: Giglio
authors.affiliation: Departments of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.affiliation: Austin Brain Tumor Center, Austin, USA.
authors.forename: M
authors.initials: M
authors.lastname: Groves
authors.affiliation: Department of Neurology, NorthShore University Health System, Evanston, USA.
authors.forename: R
authors.initials: R
authors.lastname: Merrell
authors.affiliation: Austin Brain Tumor Center, Austin, USA.
authors.forename: C
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Departments of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA.
authors.forename: S
authors.initials: S
authors.lastname: Phuphanich
authors.affiliation: James Cancer Hospital, Ohio State University, Columbus, OH, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Puduvalli
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: M
authors.initials: M
authors.lastname: Loghin
authors.affiliation: Department of Neurology, Rush University Medical Center, Chicago, USA.
authors.forename: N
authors.initials: N
authors.lastname: Paleologos
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Preventive Medicine, Northwestern University, Chicago, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rademaker
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Yung
authors.affiliation: Dell Medical School, The University of Texas, Austin, USA.
authors.forename: B
authors.initials: B
authors.lastname: Vaillant
authors.affiliation: Departments of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rudnick
authors.affiliation: Department of Neurology, University of Washington, Seattle, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chamberlain
authors.affiliation: Department of Neurology, NorthShore University Health System, Evanston, USA.
authors.forename: N
authors.initials: N
authors.lastname: Vick
authors.affiliation: Department of Neurology, Northwestern University, 710 North Lake Shore Drive, Abbott Hall, Room 1123, Chicago, IL, 60611, USA.
authors.forename: S
authors.initials: S
authors.lastname: Grimm
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: I W
authors.initials: IW
authors.lastname: Tremont-Lukats
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: J
authors.initials: J
authors.lastname: De Groot
authors.affiliation: Department of Pathology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Aldape
authors.affiliation: Neuro-Oncology Branch, NIH, Bethesda, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Gilbert
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011878:Radiotherapy / Q000009:adverse effects*; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068258:Bevacizumab; D003606:Dacarbazine; D000069347:Erlotinib Hydrochloride; D015254:DNA Modification Methylases; D000077204:Temozolomide