Kathryn M Field1, John Simes1, Anna K Nowak1, Lawrence Cher1, Helen Wheeler1, Elizabeth J Hovey1, Christopher S B Brown1, Elizabeth H Barnes1, Kate Sawkins1, Ann Livingstone1, Ron Freilich1, Pramit M Phal1, Greg Fitt1, Mark A Rosenthal1. 1. Royal Melbourne Hospital, Parkville, Australia (K.M.F, P.M.P, M.A.R.), National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (J.S., C.S.B.B., E.H.B, K.S., A.L.); Sir Charles Gairdner Hospital, Nedlands, Australia (A.K.N); School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia (A.K.N); Austin Health, Heidelberg, Australia (L.C., G.F.); Royal North Shore Hospital, St Leonards, Australia (H.W.); Prince of Wales Hospital, Randwick, Australia (E.J.H); University of New South Wales, Sydney, Australia (E.J.H); Monash Medical Centre, Clayton, Australia (R.F.); Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia (P.M.P., M.A.R., G.F.).
Abstract
BACKGROUND: The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy. METHODS: This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS). RESULTS:One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately. CONCLUSIONS: Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated withbevacizumab were inferior to those in previously reported studies. CLINICAL TRIALS REGISTRATION NR: ACTRN12610000915055.
RCT Entities:
BACKGROUND: The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy. METHODS: This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS). RESULTS: One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately. CONCLUSIONS: Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies. CLINICAL TRIALS REGISTRATION NR: ACTRN12610000915055.
Authors: Alessandra B Francesconi; Simon Dupre; Marco Matos; David Martin; Brett G Hughes; David K Wyld; Jason D Lickliter Journal: J Clin Neurosci Date: 2010-06-11 Impact factor: 1.961
Authors: Jeffrey J Raizer; Sean Grimm; Marc C Chamberlain; M Kelly Nicholas; James P Chandler; Kenji Muro; Steven Dubner; Alfred W Rademaker; Jaclyn Renfrow; Markus Bredel Journal: Cancer Date: 2010-11-15 Impact factor: 6.860
Authors: James J Vredenburgh; Annick Desjardins; James E Herndon; Jennifer Marcello; David A Reardon; Jennifer A Quinn; Jeremy N Rich; Sith Sathornsumetee; Sridharan Gururangan; John Sampson; Melissa Wagner; Leighann Bailey; Darell D Bigner; Allan H Friedman; Henry S Friedman Journal: J Clin Oncol Date: 2007-10-20 Impact factor: 44.544
Authors: Teri N Kreisl; Lyndon Kim; Kraig Moore; Paul Duic; Cheryl Royce; Irene Stroud; Nancy Garren; Megan Mackey; John A Butman; Kevin Camphausen; John Park; Paul S Albert; Howard A Fine Journal: J Clin Oncol Date: 2008-12-29 Impact factor: 44.544
Authors: Tracy T Batchelor; Paul Mulholland; Bart Neyns; L Burt Nabors; Mario Campone; Antje Wick; Warren Mason; Tom Mikkelsen; Surasak Phuphanich; Lynn S Ashby; John Degroot; Rao Gattamaneni; Lawrence Cher; Mark Rosenthal; Franz Payer; Juliane M Jürgensmeier; Rakesh K Jain; A Gregory Sorensen; John Xu; Qi Liu; Martin van den Bent Journal: J Clin Oncol Date: 2013-08-12 Impact factor: 44.544
Authors: Evanthia Galanis; S Keith Anderson; Erin L Twohy; Xiomara W Carrero; Jesse G Dixon; David Dinh Tran; Suriya A Jeyapalan; Daniel M Anderson; Timothy J Kaufmann; Ryan W Feathers; Caterina Giannini; Jan C Buckner; Panos Z Anastasiadis; David Schiff Journal: Cancer Date: 2019-07-10 Impact factor: 6.860
Authors: Kathryn M Field; Madeleine T King; John Simes; David Espinoza; Elizabeth H Barnes; Kate Sawkins; Mark A Rosenthal; Lawrence Cher; Elizabeth Hovey; Helen Wheeler; Anna K Nowak Journal: J Neurooncol Date: 2017-05-22 Impact factor: 4.130
Authors: Vaios Hatzoglou; T Jonathan Yang; Antonio Omuro; Igor Gavrilovic; Gary Ulaner; Jennifer Rubel; Taylor Schneider; Kaitlin M Woo; Zhigang Zhang; Kyung K Peck; Kathryn Beal; Robert J Young Journal: Neuro Oncol Date: 2015-12-19 Impact factor: 12.300
Authors: E Antonio Chiocca; John S Yu; Rimas V Lukas; Isaac H Solomon; Keith L Ligon; Hiroshi Nakashima; Daniel A Triggs; David A Reardon; Patrick Wen; Brittany M Stopa; Ajay Naik; Jeremy Rudnick; Jethro L Hu; Priya Kumthekar; Bakhtiar Yamini; Jill Y Buck; Nathan Demars; John A Barrett; Arnold B Gelb; John Zhou; Francois Lebel; Laurence J N Cooper Journal: Sci Transl Med Date: 2019-08-14 Impact factor: 17.956
Authors: Eudocia Q Lee; Peixin Zhang; Patrick Y Wen; Elizabeth R Gerstner; David A Reardon; Kenneth D Aldape; John F deGroot; Edward Pan; Jeffrey J Raizer; Lyndon J Kim; Steven J Chmura; H Ian Robins; Jennifer M Connelly; James D Battiste; John L Villano; Naveed Wagle; Ryan T Merrell; Merideth M Wendland; Minesh P Mehta Journal: Cancer Date: 2020-03-10 Impact factor: 6.860