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A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE)
BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS: This...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229248/ https://www.ncbi.nlm.nih.gov/pubmed/31844890 http://dx.doi.org/10.1093/neuonc/noz232 |
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author | Cloughesy, Timothy F Brenner, Andrew de Groot, John F Butowski, Nicholas A Zach, Leor Campian, Jian L Ellingson, Benjamin M Freedman, Laurence S Cohen, Yael C Lowenton-Spier, Noa Rachmilewitz Minei, Tamar Fain Shmueli, Shifra Wen, Patrick Y |
author_facet | Cloughesy, Timothy F Brenner, Andrew de Groot, John F Butowski, Nicholas A Zach, Leor Campian, Jian L Ellingson, Benjamin M Freedman, Laurence S Cohen, Yael C Lowenton-Spier, Noa Rachmilewitz Minei, Tamar Fain Shmueli, Shifra Wen, Patrick Y |
author_sort | Cloughesy, Timothy F |
collection | PubMed |
description | BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 10(13) viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS). RESULTS: Enrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91–1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3–5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction. CONCLUSIONS: In this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results. CLINICAL TRIALS REGISTRATION: NCT02511405 |
format | Online Article Text |
id | pubmed-7229248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72292482020-05-21 A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) Cloughesy, Timothy F Brenner, Andrew de Groot, John F Butowski, Nicholas A Zach, Leor Campian, Jian L Ellingson, Benjamin M Freedman, Laurence S Cohen, Yael C Lowenton-Spier, Noa Rachmilewitz Minei, Tamar Fain Shmueli, Shifra Wen, Patrick Y Neuro Oncol Clinical Investigations BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 10(13) viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS). RESULTS: Enrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91–1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3–5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction. CONCLUSIONS: In this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results. CLINICAL TRIALS REGISTRATION: NCT02511405 Oxford University Press 2020-05 2019-12-07 /pmc/articles/PMC7229248/ /pubmed/31844890 http://dx.doi.org/10.1093/neuonc/noz232 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Investigations Cloughesy, Timothy F Brenner, Andrew de Groot, John F Butowski, Nicholas A Zach, Leor Campian, Jian L Ellingson, Benjamin M Freedman, Laurence S Cohen, Yael C Lowenton-Spier, Noa Rachmilewitz Minei, Tamar Fain Shmueli, Shifra Wen, Patrick Y A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) |
title | A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) |
title_full | A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) |
title_fullStr | A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) |
title_full_unstemmed | A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) |
title_short | A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) |
title_sort | randomized controlled phase iii study of vb-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (globe) |
topic | Clinical Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229248/ https://www.ncbi.nlm.nih.gov/pubmed/31844890 http://dx.doi.org/10.1093/neuonc/noz232 |
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