Bevacizumab for glioblastoma refractory to vascular endothelial growth factor receptor inhibitors.
Glioblastoma (GBM) is a highly vascular tumor dependent on angiogenesis through the vascular endothelial growth factor (VEGF) signaling cascade. Inhibition of VEGF signaling is an important therapeutic strategy. We report our experience with bevacizumab (BEV), a VEGF targeting antibody, following failure of a VEGF receptor targeting tyrosine kinase inhibitor (TKI). We retrospectively identified patients treated on clinical trials with VEGFR-TKIs for recurrent GBM followed by BEV at next recurrence. Survival was estimated by the Kaplan-Meier method. Fourteen patients were identified (six women; median age 57). All received VEGFR-TKIs (sunitinib 11, cediranib 2, sorafenib 1) then BEV at next recurrence. There were no radiographic responses to VEGFR-TKIs; best response was stable disease in 50% (7/14). Patients received BEV alone (21%, 3/14) or in combination with chemotherapy (79%, 11/14). On BEV, 29% (4/14) had a partial response, and 36% (5/14) stabilized. Of evaluable patients, 42% (5/12) had neurological improvement and 56% (5/9) reduced corticosteroid requirement. Median survival on BEV was 7.8 months (95% CI 4.0-15.8), median progression-free survival (PFS) was 4.0 months (95% CI 1.6-10.5), and the 6-month PFS rate was 29% (95% CI 9-52). Our radiographic and survival outcomes with BEV following progression after VEGFR-TKIs are similar to data from studies of BEV as initial salvage therapy, although our sample size was small. Prior exposure to VEGFR-TKIs may not preclude response to BEV, but sensitivity to BEV may be lower following more robust VEGFR inhibition.
Department of Neurology and the Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Samuel A
SA
Goldlust
Robert
R
Cavaliere
Herbert B
HB
Newton
Meier
M
Hsu
Lisa M
LM
Deangelis
Tracy T
TT
Batchelor
Mark R
MR
Gilbert
Andrew B
AB
Lassman
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor