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Temodar, Avastin and radiation for Glioblastoma

Posted Oct 24 2009 10:04pm

Glioblastoma is a disease with a very poor prognosis. Avastin in various combinations has been studied for a number of years in this disease and Avastin aloen was FDA Apporved on April 1, 2009. Irinotecan and Avastin is NCCN recommended. REcent abstracts suggest that Avastin si also effective with Temodar in recurrent disese setting as well as upfront after resection and with radiaiton. The most convincing study, still in abstract, is by Gruber et al. From 2006–2008, 51 eligible patients (age >18, KPS >70) with newly-diagnosed GBM divided into two groups. Group A (n = 20) was treated with RT (60Gy) and concomitant TMZ (75mg/m2 daily for 42 days) with bevacizumab (10mg/kg every 2 weeks), 29 days following surgery, followed by up to six cycles of adjuvant TMZ (150mg/m2,daily x 7d, q28 with bevacizumab at 10mg/kg days 8 and 22 of each 28 day cycle. Group B (n = 31) received similar treatment without bevacizumab. Median PFS in Group A was 17 months compared to 7 months in Group B (p < 0.0001, HR = 0.26). Median OS has not been reached in Group A and was 17 months in Group B. One and 2 year OS were 83% and 57% in Group A compared to 72% and 6.5% in Group B (p = 0.02) ). Post-RT and temodar toxicities include thrombocytopenia (1 patient; Gr 3 and fatigue (3 patient;1 Gr 3), bevacizumab related toxicities with RT include leg ulcer with cellulites (1 patient; Gr 3) and pulmonary embolism with thrombocytopenia (1 patient; Gr 4), hypertension (2 patients; Gr 1), and asymptomatic blood products on MRI (2 patients).

This study overturns the previous standard of care, Temodar with radiation alone.

J R. Maron, J. J. Vredenburgh, A. Desjardins, D. A. Reardon, J. A. Quinn, J. N. Rich, S. Gururangan, S. A. Wagner, M. E. Salacz, H. S. Friedman Bevacizumab and daily temozolomide for recurrent glioblastoma multiforme (GBM).  Clin Oncol 26: 2008 (May 20 suppl; abstr 2074)

A. Lai, P. Nghiemphu, R. Green, L. Spier, S. Peak, S. Phuphanich, L. Fehrenbacher, T. Kolevska, J. Polikoff, T. Cloughesy; Phase II trial of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme, CA J Clin Oncol 27:15s, 2009 (suppl; abstr 2000)

Gruber, M. L., Raza, S., Gruber, D., Narayana, A.
Bevacizumab in combination with radiotherapy plus concomitant and adjuvant temozolomide for newly diagnosed glioblastoma: Update progression-free survival, overall survival, and toxicity
J Clin Oncol (Meeting Abstracts) 2009 27: 2017

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