Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors.
Agents targeting the vascular endothelial growth factor (VEGF) pathway are being used with increasing frequency in patients with recurrent high-grade glioma. The effect of more than one antiangiogenic therapy given in succession has not been established. We reviewed the efficacy of bevacizumab, a VEGF-A monoclonal antibody, in patients who progressed following prior therapy with VEGF receptor tyrosine kinase inhibitors (R-TKi). Seventy-three patients with recurrent high-grade gliomas received VEGF R-TKi (cediranib, sorafenib, pazopanib, or sunitinib) as part of phase I or II clinical trials. Twenty-four of these patients with glioblastoma progressed and received bevacizumab-containing regimens immediately after R-TKi. Those who stopped R-TKi therapy for reasons other than disease progression, or received a treatment that did not include bevacizumab, were excluded from the analysis. The efficacy of bevacizumab-containing regimens in these 24 patients was evaluated. During R-TKi therapy, 6 of 24 patients (25%) had a partial response (PR) to treatment. The 6-month progression-free survival (APF6) was 16.7% and median time-to-progression (TTP) was 14.3 weeks. Grade III/IV toxicities were seen in 13 of 24 patients (54%). Subsequently with bevacizumab salvage therapy, 5 of 24 patients (21%) had a PR, the APF6 was 12.5%, and the median TTP was 8 weeks. Five of 24 patients had grade III/IV toxicities (21%). The median overall survival (OS) from the start of R-TKi therapy was 9.2 months (range: 2.8-34.1+), whereas the median OS after bevacizumab was 5.2 months (range: 1.3-28.9+). Bevacizumab retains modest activity in high-grade glioma patients who progress on R-TKi. However, the APF6 of 12.5% in this cohort of patients indicates that durable tumor control is not achieved for most patients.
Lahey Clinic Medical Center, Department of Neurology, 41 Mall Road, Burlington, MA 01805, USA. brian.j.scott@lahey.org
Brian J
BJ
Scott
Eudocia C
EC
Quant
Margaret B
MB
McNamara
Peter A
PA
Ryg
Tracy T
TT
Batchelor
Patrick Y
PY
Wen
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor