Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma

作者：David A. Reardon, Alba Ariela Brandes, Antonio M. P. Omuro, Paul James Mulholland, Michael K. Lim, Antje Wick, Joachim M. Baehring, Manmeet Singh Ahluwalia, Patrick A. Roth, Oliver Bähr, Surasak Phuphanich, Juan Manuel Sepúlveda-Sánchez, Paul de Souza, Solmaz Sahebjam, Michael O. Carleton, Kay S. Tatsuoka, Corina Candiani Taitt, Ricardo F. Zwirtes, John Howard Sampson, Michael Weller · 发表于：JAMA Oncology · 年份：2020 · DOI：10.1001/jamaoncol.2020.1024 · 被引用次数：1528 · 研究领域：Glioma Diagnosis and Treatment、Cancer Immunotherapy and Biomarkers、Brain Metastases and Treatment

Importance: Clinical outcomes for glioblastoma remain poor. Treatment with immune checkpoint blockade has shown benefits in many cancer types. To our knowledge, data from a randomized phase 3 clinical trial evaluating a programmed death-1 (PD-1) inhibitor therapy for glioblastoma have not been reported. Objective: To determine whether single-agent PD-1 blockade with nivolumab improves survival in patients with recurrent glioblastoma compared with bevacizumab. Design, Setting, and Participants: In this open-label, randomized, phase 3 clinical trial, 439 patients with glioblastoma at first recurrence following standard radiation and temozolomide therapy were enrolled, and 369 were randomized. Patients were enrolled between September 2014 and May 2015. The median follow-up was 9.5 months at data cutoff of January 20, 2017. The study included 57 multicenter, multinational clinical sites. Interventions: Patients were randomized 1:1 to nivolumab 3 mg/kg or bevacizumab 10 mg/kg every 2 weeks until confirmed disease progression, unacceptable toxic effects, or death. Main Outcomes and Measures: The primary end point was overall survival (OS). Results: A total of 369 patients were randomized to nivolumab (n = 184) or bevacizumab (n = 185). The MGMT promoter was methylated in 23.4% (43/184; nivolumab) and 22.7% (42/185; bevacizumab), unmethylated in 32.1% (59/184; nivolumab) and 36.2% (67/185; bevacizumab), and not reported in remaining patients. At median follow-up of 9.5 months, media...