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NEUROLOGY 2009;73:1200-1206
© 2009 American Academy of Neurology

Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma

F. M. Iwamoto, MD, L. E. Abrey, MD, K. Beal, MD, P. H. Gutin, MD, M. K. Rosenblum, MD, V. E. Reuter, MD, L. M. DeAngelis, MD and A. B. Lassman, MD

From the Departments of Neurology (F.M.I., L.E.A., L.M.D., A.B.L.), Radiation Oncology (K.B.), Neurosurgery (P.H.B.), and Pathology (M.K.R., V.E.R.) and the Brain Tumor Center (F.M.I., L.E.A., K.B., P.H.G., M.K.R., L.M.D., A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, NYI. is currently with the Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD.

Address correspondence and reprint requests to Dr. Andrew B. Lassman, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065 lassmana{at}mskcc.org

Background: Bevacizumab has recently been approved by the US Food and Drug Administration for recurrent glioblastoma (GBM). However, patterns of relapse, prognosis, and outcome of further therapy after bevacizumab failure have not been studied systematically.

Methods: We identified patients at Memorial Sloan-Kettering Cancer Center with recurrent GBM who discontinued bevacizumab because of progressive disease.

Results: There were 37 patients (26 men with a median age of 54 years). The most common therapies administered concurrently with bevacizumab were irinotecan (43%) and hypofractionated reirradiation (38%). The median overall survival (OS) after progressive disease on bevacizumab was 4.5 months; 34 patients died. At the time bevacizumab was discontinued for tumor progression, 17 patients (46%) had an increase in the size of enhancement at the initial site of disease (local recurrence), 6 (16%) had a new enhancing lesion outside of the initial site of disease (multifocal), and 13 (35%) had progression of predominantly nonenhancing tumor. Factors associated with shorter OS after discontinuing bevacizumab were lower performance status and nonenhancing pattern of recurrence. Additional salvage chemotherapy after bevacizumab failure was given to 19 patients. The median progression-free survival (PFS) among these 19 patients was 2 months, the median OS was 5.2 months, and the 6-month PFS rate was 0%.

Conclusions: Contrast enhanced MRI does not adequately assess disease status during bevacizumab therapy for recurrent glioblastoma (GBM). A nonenhancing tumor pattern of progression is common after treatment with bevacizumab for GBM and is correlated with worse survival. Treatments after bevacizumab failure provide only transient tumor control.

Abbreviations: CA9 = carbonic anhydrase 9; CI = confidence interval; FDG = [18F]fluorodeoxyglucose; FLAIR = fluid-attenuation inversion recovery; GBM = glioblastoma; HIF-1{alpha} = hypoxia-inducible factor 1{alpha}; KPS = Karnofsky performance status; MR = magnetic resonance; OS = overall survival; PFS = progression-free survival; TMZ = temozolomide; VEGF = vascular endothelial growth factor; VEGFR = vascular endothelial growth factor receptor.

Disclosure: Author disclosures are provided at the end of the article.

Presented in part at the American Society of Clinical Oncology Annual Meeting, May 30–June 3, 2008, Chicago, IL.

Received March 13, 2009. Accepted in final form July 7, 2009.






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