BTTC08-01: A phase II study of bevacizumab and erlotinib after radiation therapy and temozolomide in patients with newly diagnosed glioblastoma (GBM) without MGMT promoter methylation.

Central Nervous System Tumors
Session Type and Session Title: 
Poster Discussion Session, Central Nervous System Tumors
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 2019^)
Jeffrey J. Raizer, Pierre Giglio, Jethro Lisien Hu, Morris D. Groves, Ryan Merrell, Charles A. Conrad, Surasak Phuphanich, Vinay K. Puduvalli, Monica Elena Loghin, Nina Paleologos, W. K. Alfred Yung, Brian D. Vaillant, Jeremy David Rudnick, Marc C. Chamberlain, Nicholas Vick, Sean Aaron Grimm, Ivo Tremont-Lukats, John Frederick De Groot, Kenneth D. Aldape, Mark R. Gilbert; Northwestern University, Feinberg School of Medicine, Chicago, IL; MUSC Hollings Cancer Center, Charleston, SC; Cedars-Sinai Medical Center, Los Angeles, CA; Texas Oncology, Austin, TX; Northshore University, Evanston, IL; The University of Texas MD Anderson Cancer Center, Houston, TX; Neuro-Oncology Program, Cedars-Sinai Medical Center, Los Angeles, CA; Rush University, Chicago, IL; The Methodist Hospital, Houston, TX; University of Washington, Seattle, WA; University of Minnesota, Minneapolis, MN; The University of Texas M.D. Anderson Cancer Center, Houston, TX

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Abstract Disclosures


Background: Patients (pts) with GBM with unmethylated MGMT have a worse prognosis than those with methylated MGMT. Novel approaches for this poor risk group are warranted. The Brain Tumor Trials Collaborative (BTTC) performed a phase II trial evaluating standard chemoradiation followed by bevacizumab and erlotinib in patients with MGMT unmethylated GBM. EGFR and VEGFR are upregulated during radiation suggesting that this combination could be more effective than post-radiation adjuvant temozolomide (TMZ). Methods: After informed consent, adult patients with supratentorial GBM, KPS ≥ 70 and > 1 cm2 tumor block for MGMT promoter analysis were screened. Only tumors with confirmed unmethylated MGMT promoter were enrolled. All patients received RT + TMZ and then approximately 4 weeks after RT they received bevacizumab 10 mg/kg every 2 weeks and erlotinib 150 mg/day, continuously. One cycle was 4 weeks; evaluation by MRI was every 2 cycles. Treatment continued until disease progression or intolerable adverse events. Results: 115 patients were screened; 48 were enrolled (2 unevaluable: 1 for an infratentoral GBM and 1 withdrew after 7 days of treatment) with 29 men, 17 women. Median age was 56 yrs (29-75); median KPS was 90 (70-90). The median number of cycles was 8 (2-38) with 4 patients remaining on trial at the time of analysis. Objective responses: 4 CR, 12 PR and 30 SD. Median PFS is 7.3 months (95% CI (6.4, 11)) and median OS 14.2 months (95% CI (10.7, not reached)). There were no unexpected toxicities; grade 3/4 rate < 5%. Conclusions: Adjuvant bevacizumab and erlotinib in GBM with unmethylated MGMT is well tolerated. Preliminary efficacy data is comparable with outcomes in similar unmethylated MGMT patient populations from the EORTC/NCIC and RTOG 0525 studies. Tissue correlation is being performed. Clinical trial information: NCT00720356.