title: An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma.
abstract: Recent clinical trial results suggest that anti-angiogenic therapy may be effective against recurrent malignant glioma. Though these treatments prolong progression-free survival, the extent to which they prolong overall survival is unknown. We pooled data from 34 patients treated at a single institution on phase II clinical trials of bevacizumab and cediranib, and we compared these data to 18 patients treated on clinical trials of cytotoxic chemotherapies. In univariate and multivariate analyses, treatment group was a significant predictor of progression-free but not overall survival. Median progression-free survival was 8 vs. 22 weeks in patients treated with cytotoxic as compared to anti-angiogenic therapy (P = 0.01). Median overall survival was nearly identical in the two groups (39 vs. 37 weeks). The results of this exploratory analysis suggest that anti-angiogenic therapy may fail to prolong overall survival in patients with recurrent malignant glioma. If this conclusion proves correct, progression-free survival may be an inappropriate endpoint for phase II trials of anti-angiogenic therapies.
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. anorden@partners.org
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Norden
authors.forename: Jan
authors.initials: J
authors.lastname: Drappatz
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Karly
authors.initials: K
authors.lastname: David
authors.forename: Mary
authors.initials: M
authors.lastname: Gerard
authors.forename: M Brenna
authors.initials: MB
authors.lastname: McNamara
authors.forename: Phuong
authors.initials: P
authors.lastname: Phan
authors.forename: Ainsley
authors.initials: A
authors.lastname: Ross
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002227:Carbazoles / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D011799:Quinazolines / Q000008:administration & dosage; D016019:Survival Analysis; D007211:Indoles
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002166:Camptothecin; D002227:Carbazoles; D011799:Quinazolines; C433984:ST 1481; C121395:edotecarin; C500926:cediranib; D007211:Indoles