A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE)
| Autor: | Jian Campian, Andrew Brenner, Patrick Y. Wen, Shifra Fain Shmueli, John de Groot, Tamar Rachmilewitz Minei, Laurence S. Freedman, Noa Lowenton-Spier, Leor Zach, Nicholas Butowski, Timothy F. Cloughesy, Benjamin M. Ellingson, Yael C Cohen |
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| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
medicine.medical_specialty Bevacizumab business.industry Hazard ratio Phases of clinical research Gastroenterology law.invention Oncology Randomized controlled trial law Concomitant Internal medicine medicine Clinical endpoint In patient Neurology (clinical) business Adverse effect medicine.drug |
| Zdroj: | Neuro-Oncology. 22:705-717 |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/noz232 |
| Popis: | BackgroundOfranergene 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.MethodsThis 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 1013 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).ResultsEnrolled 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.ConclusionsIn 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 registrationNCT02511405 |
| Databáze: | OpenAIRE |
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