Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial

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. To dete...

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Vydané v:	JAMA oncology Ročník 6; číslo 7; s. 1003
Hlavní autori:	Reardon, David A, Brandes, Alba A, Omuro, Antonio, Mulholland, Paul, Lim, Michael, Wick, Antje, Baehring, Joachim, Ahluwalia, Manmeet S, Roth, Patrick, Bähr, Oliver, Phuphanich, Surasak, Sepulveda, Juan Manuel, De Souza, Paul, Sahebjam, Solmaz, Carleton, Michael, Tatsuoka, Kay, Taitt, Corina, Zwirtes, Ricardo, Sampson, John, Weller, Michael
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.07.2020
Predmet:	Adult Aged Angiogenesis Inhibitors - adverse effects Angiogenesis Inhibitors - therapeutic use Antineoplastic Agents, Immunological - adverse effects Antineoplastic Agents, Immunological - therapeutic use Bevacizumab - adverse effects Bevacizumab - therapeutic use Brain Neoplasms - drug therapy Brain Neoplasms - genetics Brain Neoplasms - mortality Brain Neoplasms - radiotherapy DNA Modification Methylases - genetics DNA Repair Enzymes - genetics Female Glioblastoma - drug therapy Glioblastoma - genetics Glioblastoma - mortality Glioblastoma - radiotherapy Humans Immune Checkpoint Inhibitors - adverse effects Immune Checkpoint Inhibitors - therapeutic use Male Middle Aged Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - mortality Nivolumab - adverse effects Nivolumab - therapeutic use Programmed Cell Death 1 Receptor - antagonists & inhibitors Temozolomide - therapeutic use Treatment Outcome Tumor Suppressor Proteins - genetics Young Adult
ISSN:	2374-2445, 2374-2445
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Shrnutí:	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. To determine whether single-agent PD-1 blockade with nivolumab improves survival in patients with recurrent glioblastoma compared with bevacizumab. 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. 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. The primary end point was overall survival (OS). 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, median OS (mOS) was comparable between groups: nivolumab, 9.8 months (95% CI, 8.2-11.8); bevacizumab, 10.0 months (95% CI, 9.0-11.8); HR, 1.04 (95% CI, 0.83-1.30); P = .76. The 12-month OS was 42% in both groups. The objective response rate was higher with bevacizumab (23.1%; 95% CI, 16.7%-30.5%) vs nivolumab (7.8%; 95% CI, 4.1%-13.3%). Grade 3/4 treatment-related adverse events (TRAEs) were similar between groups (nivolumab, 33/182 [18.1%]; bevacizumab, 25/165 [15.2%]), with no unexpected neurological TRAEs or deaths due to TRAEs. Although the primary end point was not met in this randomized clinical trial, mOS was comparable between nivolumab and bevacizumab in the overall patient population with recurrent glioblastoma. The safety profile of nivolumab in patients with glioblastoma was consistent with that in other tumor types. ClinicalTrials.gov Identifier: NCT02017717.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	2374-2445 2374-2445
DOI:	10.1001/jamaoncol.2020.1024