Elizabeth J Hovey1, Kathryn M Field1, Mark A Rosenthal1, Elizabeth H Barnes1, Lawrence Cher1, Anna K Nowak1, Helen Wheeler1, Kate Sawkins1, Ann Livingstone1, Pramit Phal1, Christine Goh1, John Simes1. 1. Prince of Wales Hospital, Barker Street, Randwick, Sydney, NSW 2031, Australia (E.J.H.); University of New South Wales, Sydney, NSW 2052, Australia (E.J.H.); Royal Melbourne Hospital, Grattan Street, Parkville 3050, Melbourne Victoria, Australia (K.M.F., M.A.R., P.P., C.G.); Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Grattan Street Parkville 3052, Victoria, Australia (K.M.F., M.A.R.); National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Sydney, NSW 2006, Australia (E.H.B., K.S., A.L., J.S.); Austin Hospital, 145 Studley Road, Heidelberg, Melbourne, Victoria 3084, Australia (L.C.); Sir Charles Gairdner Hospital, Nedlands, Perth 6009, Western Australia (A.K.N.); Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia (H.W.).
Abstract
BACKGROUND: In patients with recurrent glioblastoma, the benefit of bevacizumab beyond progression remains uncertain. We prospectively evaluated continuing or ceasing bevacizumab in patients who progressed while on bevacizumab. METHODS: CABARET, a phase II study, initially randomized patients to bevacizumab with or without carboplatin (Part 1). At progression, eligible patients underwent a second randomization to continue or cease bevacizumab (Part 2). They could also receive additional chemotherapy regimens (carboplatin, temozolomide, or etoposide) or supportive care. RESULTS: Of 120 patients treated in Part 1, 48 (80% of the anticipated 60-patient sample size) continued to Part 2. Despite randomization, there were some imbalances in patient characteristics. The best response was stable disease in 7 (30%) patients who continued bevacizumab and 2 (8%) patients who stopped receiving bevacizumab. There were no radiological responses. Median progression-free survival was 1.8 vs 2.0 months (bevacizumab vs no bevacizumab; hazard ratio [HR], 1.08; 95% CI, .59-1.96; P = .81). Median overall survival was 3.4 vs 3.0 months (HR, .84; 95% CI, .47-1.50; P = .56 and HR .70; 95% CI .38-1.29; P = .25 after adjustment for baseline factors). Quality-of-life scores did not significantly differ between arms. While the maximum daily steroid dose was lower in the continuation arm, the difference was not statistically significant. CONCLUSIONS: Patients who continued bevacizumab beyond disease progression did not have clear survival improvements, although the study was not powered to detect other than very large differences. While these data provide the only randomized evidence related to continuing bevacizumab beyond progression in recurrent glioblastoma, the small sample size precludes definitive conclusions and suggests this remains an open question.
BACKGROUND: In patients with recurrent glioblastoma, the benefit of bevacizumab beyond progression remains uncertain. We prospectively evaluated continuing or ceasing bevacizumab in patients who progressed while on bevacizumab. METHODS: CABARET, a phase II study, initially randomized patients to bevacizumab with or without carboplatin (Part 1). At progression, eligible patients underwent a second randomization to continue or cease bevacizumab (Part 2). They could also receive additional chemotherapy regimens (carboplatin, temozolomide, or etoposide) or supportive care. RESULTS: Of 120 patients treated in Part 1, 48 (80% of the anticipated 60-patient sample size) continued to Part 2. Despite randomization, there were some imbalances in patient characteristics. The best response was stable disease in 7 (30%) patients who continued bevacizumab and 2 (8%) patients who stopped receiving bevacizumab. There were no radiological responses. Median progression-free survival was 1.8 vs 2.0 months (bevacizumab vs no bevacizumab; hazard ratio [HR], 1.08; 95% CI, .59-1.96; P = .81). Median overall survival was 3.4 vs 3.0 months (HR, .84; 95% CI, .47-1.50; P = .56 and HR .70; 95% CI .38-1.29; P = .25 after adjustment for baseline factors). Quality-of-life scores did not significantly differ between arms. While the maximum daily steroid dose was lower in the continuation arm, the difference was not statistically significant. CONCLUSIONS: Patients who continued bevacizumab beyond disease progression did not have clear survival improvements, although the study was not powered to detect other than very large differences. While these data provide the only randomized evidence related to continuing bevacizumab beyond progression in recurrent glioblastoma, the small sample size precludes definitive conclusions and suggests this remains an open question.
Entities:
Keywords:
bevacizumab; carboplatin; glioblastoma; phase II trial
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