Please use this identifier to cite or link to this item: http://docs.prosentient.com.au/prosentientjspui/handle/1/11049
Title: A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma.
Authors: Brandes, Alba A
Gil-Gil, Miguel
Saran, Frank
Carpentier, Antoine F
Nowak, Anna K
Mason, Warren
Zagonel, Vittorina
Dubois, François
Finocchiaro, Gaetano
Fountzilas, George
Cernea, Dana Michaela
Chinot, Oliver
Anghel, Rodica
Ghiringhelli, Francois
Beauchesne, Patrick
Lombardi, Giuseppe
Franceschi, Enrico
Makrutzki, Martina
Mpofu, Chiedzo
Urban, Hans-Joerg
Pichler, Josef
Affiliation: Department of Medical Oncology, AUSL, Bologna, Italy alba.brandes@yahoo.it..
Institut Catala d'Oncologia, L'Hospitalet, Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Barcelona, Spain..
Royal Marsden National Health Service Foundation Trust, Sutton, United Kingdom..
Paris 7 University, Assistance publique - Hôpitaux de Paris (AP-HP), Paris, France..
School of Medicine, University of Western Australia, Crawley, Australia..
Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Canada..
Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Veneto Institute of Oncology-IRCCS, Padua, Italy..
Centre Hospitalier Régional et Universitaire de Lille, Lille, France..
Istituto Neurologico Carlo Besta, Milan, Italy..
Aristotle University of Thessaloniki, Thessaloniki, Greece..
The Oncology Institute "Prof. Dr. Ion Chiricuta," Cluj-Napoca, Romania..
Aix-Marseille University, Assistance publique - Hôpitaux de Marseille (AP-HM), CHU Timone, Marseille, France..
Alexandru Trestioreanu Bucharest Institute of Oncology, Bucharest, Romania.. Carol Davila University of Medicine and Pharmacy Bucharest, Bucharest, Romania..
Centre Georges Francois Leclerc, Dijon, France..
Département de Neuro-Oncologie, Hôpital Central, Nancy, France..
Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Veneto Institute of Oncology-IRCCS, Padua, Italy..
Department of Medical Oncology, AUSL, Bologna, Italy..
F. Hoffmann-La Roche Ltd., Basel, Switzerland..
F. Hoffmann-La Roche Ltd., Basel, Switzerland..
F. Hoffmann-La Roche Ltd., Basel, Switzerland..
Institut für Innere Medizin mit Neuroonkologie, Linz, Austria..
Issue Date: 28-Sep-2018
Citation: The oncologist 2018-09-28
Abstract: We assessed the efficacy and safety of bevacizumab (BEV) through multiple lines in patients with recurrent glioblastoma who had progressed after first-line treatment with radiotherapy, temozolomide, and BEV. TAMIGA (NCT01860638) was a phase II, randomized, double-blind, placebo-controlled, multicenter trial in adult patients with glioblastoma. Following surgery, patients with newly diagnosed glioblastoma received first-line treatment consisting of radiotherapy plus temozolomide and BEV, followed by six cycles of temozolomide and BEV, then BEV monotherapy until disease progression (PD1). Randomization occurred at PD1 (second line), and patients received lomustine (CCNU) plus BEV (CCNU + BEV) or CCNU plus placebo (CCNU + placebo) until further disease progression (PD2). At PD2 (third line), patients continued BEV or placebo with chemotherapy (investigator's choice). The primary endpoint was survival from randomization. Secondary endpoints were progression-free survival in the second and third lines (PFS2 and PFS3) and safety. Of the 296 patients enrolled, 123 were randomized at PD1 (CCNU + BEV, n = 61; CCNU + placebo, n = 62). The study was terminated prematurely because of the high drop-out rate during first-line treatment, implying underpowered inferential testing. The proportion of patients receiving corticosteroids at randomization was similar (BEV 33%, placebo 31%). For the CCNU + BEV and CCNU + placebo groups, respectively, median survival from randomization was 6.4 versus 5.5 months (stratified hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.69-1.59), median PFS2 was 2.3 versus 1.8 months (stratified HR, 0.70; 95% CI, 0.48-1.00), median PFS3 was 2.0 versus 2.2 months (stratified HR, 0.70; 95% CI, 0.37-1.33), and median time from randomization to a deterioration in health-related quality of life was 1.4 versus 1.3 months (stratified HR, 0.76; 95% CI, 0.52-1.12). The incidence of treatment-related grade 3 to 4 adverse events was 19% (CCNU + BEV) versus 15% (CCNU + placebo). There was no survival benefit and no detriment observed with continuing BEV through multiple lines in patients with recurrent glioblastoma. Previous research suggested that there may be value in continuing bevacizumab (BEV) beyond progression through multiple lines of therapy. No survival benefit was observed with the use of BEV through multiple lines in patients with glioblastoma who had progressed after first-line treatment (radiotherapy + temozolomide + BEV). No new safety concerns arose from the use of BEV through multiple lines of therapy.
URI: http://docs.prosentient.com.au/prosentientjspui/handle/1/11049
DOI: 10.1634/theoncologist.2018-0290
Type: Journal Article
Subjects: Clinical trial
Continuous bevacizumab
Overall survival
Recurrent glioblastoma
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