David E Piccioni1, Julia Selfridge1, Reema R Mody1, Reshmi Chowdhury1, Sichen Li1, Shadi Lalezari1, James Wawrzynski1, Jennifer Quan1, Mira Zurayk1, Arthur P Chou1, Desiree E Sanchez1, Linda M Liau1, Benjamin M Ellingson1, Whitney B Pope1, Phioanh L Nghiemphu1, Richard M Green1, He-Jing Wang1, William H Yong1, Robert Elashoff1, Timothy F Cloughesy1, Albert Lai1. 1. Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
Abstract
BACKGROUND: The optimal timing to initiate bevacizumab (BV) therapy for recurrent glioblastoma (GBM) is currently unclear. To address this issue, we examined progression-free survival (PFS) and survival time (ST) in a large retrospective cohort of GBM patients treated with BV at different recurrences. METHODS: We identified 468 primary GBM patients who underwent biopsy or surgery followed by radiation therapy and temozolomide (RT/TMZ), and then received BV. PFS and ST were compared between patients stratified by the recurrence that BV was initiated (upfront, first recurrence, second recurrence, or 3+ recurrences). We also examined the effect on PFS and ST of the addition of chemotherapy to BV. In a larger cohort of GBM patients, we determined overall treatment continuation rates at each recurrence and identified variables predictive of inability to continue treatment. RESULTS: BV PFS was similar for all 3 recurrence groups (median, 4.1 months). There were no differences in BV ST (median, 9.8 months). The addition of chemotherapy to BV improved PFS but not ST. Analysis of treatment continuation rates indicated that the number of patients unable to undergo further treatments is modest, and that patients unable to tolerate BV delay can be identified by age ≥60 years and low extent of resection. CONCLUSIONS: Deferred use of bevacizumab is not associated with diminished efficacy. Analysis of treatment continuation rates identified patients who may be unable to delay BV therapy. Our findings suggest that there is a fixed survival after BV initiation and that delayed BV treatment is preferable for most patients.
BACKGROUND: The optimal timing to initiate bevacizumab (BV) therapy for recurrent glioblastoma (GBM) is currently unclear. To address this issue, we examined progression-free survival (PFS) and survival time (ST) in a large retrospective cohort of GBMpatients treated with BV at different recurrences. METHODS: We identified 468 primary GBMpatients who underwent biopsy or surgery followed by radiation therapy and temozolomide (RT/TMZ), and then received BV. PFS and ST were compared between patients stratified by the recurrence that BV was initiated (upfront, first recurrence, second recurrence, or 3+ recurrences). We also examined the effect on PFS and ST of the addition of chemotherapy to BV. In a larger cohort of GBMpatients, we determined overall treatment continuation rates at each recurrence and identified variables predictive of inability to continue treatment. RESULTS:BV PFS was similar for all 3 recurrence groups (median, 4.1 months). There were no differences in BV ST (median, 9.8 months). The addition of chemotherapy to BV improved PFS but not ST. Analysis of treatment continuation rates indicated that the number of patients unable to undergo further treatments is modest, and that patients unable to tolerate BV delay can be identified by age ≥60 years and low extent of resection. CONCLUSIONS: Deferred use of bevacizumab is not associated with diminished efficacy. Analysis of treatment continuation rates identified patients who may be unable to delay BV therapy. Our findings suggest that there is a fixed survival after BV initiation and that delayed BV treatment is preferable for most patients.
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