{"doi":"10.1093/neuonc/noaa062","title":"A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with recurrent glioblastoma","abstract":"BACKGROUND: Bevacizumab has promising activity against recurrent glioblastoma (GBM). However, acquired resistance to this agent results in tumor recurrence. We hypothesized that vorinostat, a histone deacetylase (HDAC) inhibitor with anti-angiogenic effects, would prevent acquired resistance to bevacizumab. METHODS: This multicenter phase II trial used a Bayesian adaptive design to randomize patients with recurrent GBM to bevacizumab alone or bevacizumab plus vorinostat with the primary endpoint of progression-free survival (PFS) and secondary endpoints of overall survival (OS) and clinical outcomes assessment (MD Anderson Symptom Inventory Brain Tumor module [MDASI-BT]). Eligible patients were adults (≥18 y) with histologically confirmed GBM recurrent after prior radiation therapy, with adequate organ function, KPS ≥60, and no prior bevacizumab or HDAC inhibitors. RESULTS: Ninety patients (bevacizumab + vorinostat: 49, bevacizumab: 41) were enrolled, of whom 74 were evaluable for PFS (bevacizumab + vorinostat: 44, bevacizumab: 30). Median PFS (3.7 vs 3.9 mo, P = 0.94, hazard ratio [HR] 0.63 [95% CI: 0.38, 1.06, P = 0.08]), median OS (7.8 vs 9.3 mo, P = 0.64, HR 0.93 [95% CI: 0.5, 1.6, P = 0.79]) and clinical benefit were similar between the 2 arms. Toxicity (grade ≥3) in 85 evaluable patients included hypertension (n = 37), neurological changes (n = 2), anorexia (n = 2), infections (n = 9), wound dehiscence (n = 2), deep vein thrombosis/pulmonary embolism (n = 2), and colonic perforation (n = 1). CONCLUSIONS: Bevacizumab combined with vorinostat did not yield improvement in PFS or OS or clinical benefit compared with bevacizumab alone or a clinical benefit in adults with recurrent GBM. This trial is the first to test a Bayesian adaptive design with adaptive randomization and Bayesian continuous monitoring in patients with primary brain tumor and demonstrates the feasibility of using complex Bayesian adaptive design in a multicenter setting.","journal":"Neuro-Oncology","year":2020,"id":91068,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":46,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9448,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":456431,"name":"Jing Wu","orcid":"0000-0001-5803-7402","position":1,"is_corresponding":false},{"id":268557,"name":"Ying Yuan","orcid":"0000-0003-3163-480X","position":2,"is_corresponding":false},{"id":292546,"name":"Terri S. Armstrong","orcid":"0000-0002-2414-0492","position":3,"is_corresponding":false},{"id":292544,"name":"Elizabeth Vera","orcid":"0000-0001-7604-2555","position":4,"is_corresponding":false},{"id":311442,"name":"Jimin Wu","orcid":"0000-0001-6383-9020","position":5,"is_corresponding":false},{"id":456432,"name":"Jihong Xu","orcid":"0000-0002-1177-8315","position":6,"is_corresponding":false},{"id":456433,"name":"Pierre Giglio","orcid":"0000-0001-5165-0984","position":7,"is_corresponding":false},{"id":69888,"name":"Howard Colman","orcid":"0000-0002-4027-7317","position":8,"is_corresponding":false},{"id":456434,"name":"Tobias Walbert","orcid":"0000-0003-0667-8106","position":9,"is_corresponding":false},{"id":273503,"name":"Jeffrey J. Raizer","orcid":"0009-0003-8469-2509","position":10,"is_corresponding":false},{"id":296953,"name":"Morris D. Groves","orcid":null,"position":11,"is_corresponding":false},{"id":457855,"name":"David Tran","orcid":null,"position":12,"is_corresponding":false},{"id":314263,"name":"Fábio M. Iwamoto","orcid":"0000-0003-1397-9927","position":13,"is_corresponding":false},{"id":457856,"name":"Nicholas G. Avgeropoulos","orcid":null,"position":14,"is_corresponding":false},{"id":457857,"name":"Nina A. Paleologos","orcid":null,"position":15,"is_corresponding":false},{"id":457858,"name":"Karen Fink","orcid":null,"position":16,"is_corresponding":false},{"id":255947,"name":"David M. Peereboom","orcid":"0000-0001-7798-5176","position":17,"is_corresponding":false},{"id":456435,"name":"Marc C. Chamberlain","orcid":"0000-0002-1613-1123","position":18,"is_corresponding":false},{"id":456436,"name":"Ryan Merrell","orcid":"0000-0002-8076-0768","position":19,"is_corresponding":false},{"id":457859,"name":"Marta Penas Prado","orcid":null,"position":20,"is_corresponding":false},{"id":365488,"name":"W.K. Alfred Yung","orcid":null,"position":21,"is_corresponding":false},{"id":109755,"name":"Mark R. Gilbert","orcid":"0000-0003-2556-9722","position":22,"is_corresponding":false},{"id":225612,"name":"Vinay K. Puduvalli","orcid":"0000-0001-8396-9500","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T22:28:45.409789Z","pmid":"32166308","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}