Alba A Brandes1, Gaetano Finocchiaro2, Vittorina Zagonel2, Michele Reni2, Claudia Caserta2, Alessandra Fabi2, Matteo Clavarezza2, Evaristo Maiello2, Marica Eoli2, Giuseppe Lombardi2, Marta Monteforte2, Emanuela Proietti2, Raffaele Agati2, Vincenzo Eusebi2, Enrico Franceschi2. 1. Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Bologna, Italy (A.A.B., E.F.); Molecular Neuro-Oncology Unit, IRCCS Foundation Carlo Besta, Milan, Italy (G.F., M.E.); Department of Clinical and Experimental Oncology, Medical Oncology, Veneto Institute of Oncology- IRCCS Padua, Italy (V.Z., G.L.); Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy (M.R.); Oncology Department, Santa Maria Hospital, Terni, Italy (C.C.); Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy (A.F.); E.O. Ospedale Galliera, Genova, Italy (M.C.); Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (E.M.); OPIS, Palazzo Aliprandi, Desio MB, Italy (M.M.); Roche S.p.A. Medical Affairs and CO, Monza, Italy (E.P.); Neuroradiology Department, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Ospedale Bellaria, Bologna, Italy (R.A.); Department of Biomedical and Neuromotor Science, University of Bologna, Section of Anatomic Pathology M. Malpighi-Bellaria Hospital, Bologna, Italy (V.E.) alba.brandes@yahoo.it. 2. Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Bologna, Italy (A.A.B., E.F.); Molecular Neuro-Oncology Unit, IRCCS Foundation Carlo Besta, Milan, Italy (G.F., M.E.); Department of Clinical and Experimental Oncology, Medical Oncology, Veneto Institute of Oncology- IRCCS Padua, Italy (V.Z., G.L.); Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy (M.R.); Oncology Department, Santa Maria Hospital, Terni, Italy (C.C.); Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy (A.F.); E.O. Ospedale Galliera, Genova, Italy (M.C.); Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (E.M.); OPIS, Palazzo Aliprandi, Desio MB, Italy (M.M.); Roche S.p.A. Medical Affairs and CO, Monza, Italy (E.P.); Neuroradiology Department, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Ospedale Bellaria, Bologna, Italy (R.A.); Department of Biomedical and Neuromotor Science, University of Bologna, Section of Anatomic Pathology M. Malpighi-Bellaria Hospital, Bologna, Italy (V.E.).
Abstract
BACKGROUND: Few prospective studies have assessed the role of bevacizumab and included a control arm with standard treatments for recurrent glioblastoma. We conducted a noncomparative phase II trial (AVAREG) to examine the efficacy of bevacizumab or fotemustine in this setting. METHODS:Eligible patients were randomized 2:1 to receive bevacizumab (10 mg/kg every 2 weeks) or fotemustine (75 mg/m(2) on days 1, 8, and 15, then 100 mg/m(2) every 3 weeks after a 35-day interval). The primary endpoint was 6-month overall survival (OS) rate (OS-6). No formal efficacy comparison was made between the treatment arms. RESULTS:Ninety-one patients were enrolled (bevacizumab n = 59; fotemustine n = 32). Median age was 57 years (range, 28-78 y), and patients had Eastern Cooperative Oncology Group performance status of 0 (n = 42), 1 (n = 35), or 2 (n = 14). OS-6 rate was 62.1% (95% confidence interval [CI], 48.4-74.5) with bevacizumab and 73.3% (95% CI, 54.1-87.7) with fotemustine. OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors (50% and 85%, respectively), but higher in fotemustine-treated patients (87.5% and 50%, respectively). OS rates at 9 months were 37.9% (95% CI, 25.5-51.6) and 46.7% (95% CI, 28.3-65.7) with bevacizumab and fotemustine, respectively, and median OS was 7.3 months (95% CI, 5.8-9.2) and 8.7 months (95% CI, 6.3-15.4), respectively. Toxicity was as expected with the 2 agents. CONCLUSION:Single-agent bevacizumab may have a role in patients with recurrent glioblastoma.
RCT Entities:
BACKGROUND: Few prospective studies have assessed the role of bevacizumab and included a control arm with standard treatments for recurrent glioblastoma. We conducted a noncomparative phase II trial (AVAREG) to examine the efficacy of bevacizumab or fotemustine in this setting. METHODS: Eligible patients were randomized 2:1 to receive bevacizumab (10 mg/kg every 2 weeks) or fotemustine (75 mg/m(2) on days 1, 8, and 15, then 100 mg/m(2) every 3 weeks after a 35-day interval). The primary endpoint was 6-month overall survival (OS) rate (OS-6). No formal efficacy comparison was made between the treatment arms. RESULTS: Ninety-one patients were enrolled (bevacizumab n = 59; fotemustine n = 32). Median age was 57 years (range, 28-78 y), and patients had Eastern Cooperative Oncology Group performance status of 0 (n = 42), 1 (n = 35), or 2 (n = 14). OS-6 rate was 62.1% (95% confidence interval [CI], 48.4-74.5) with bevacizumab and 73.3% (95% CI, 54.1-87.7) with fotemustine. OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors (50% and 85%, respectively), but higher in fotemustine-treated patients (87.5% and 50%, respectively). OS rates at 9 months were 37.9% (95% CI, 25.5-51.6) and 46.7% (95% CI, 28.3-65.7) with bevacizumab and fotemustine, respectively, and median OS was 7.3 months (95% CI, 5.8-9.2) and 8.7 months (95% CI, 6.3-15.4), respectively. Toxicity was as expected with the 2 agents. CONCLUSION: Single-agent bevacizumab may have a role in patients with recurrent glioblastoma.
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