TY  - JOUR
A1  - Omuro, Antonio
A1  - Brandes, Alba
A1  - Carpentier, Antoine
A1  - Idbaih, Ahmed
A1  - Reardon, David A.
A1  - Cloughesy, Timothy
A1  - Sumrall, Ashley
A1  - Bähring, Joachim
A1  - Van den Bent, Martin J.
A1  - Bähr, Roy Oliver
A1  - Lombardi, Giuseppe
A1  - Mulholland, Paul
A1  - Tabatabai, Ghazaleh
A1  - Lassen, Ulrik
A1  - Sepúlveda, Juan Manuel
A1  - Khasraw, Mustafa
A1  - Vauleon, Elodie
A1  - Muragaki, Yoshihiro
A1  - Di Giacomo, Anna Maria
A1  - Butowski, Nicholas
A1  - Roth, Patrick
A1  - Qian, Xiaozhong
A1  - Fu, Alex Z.
A1  - Liu, Yanfang
A1  - Potter, Von
A1  - Chalamandaris, Alexandros-Georgios
A1  - Tatsuoka, Kay
A1  - Lim, Michael
A1  - Weller, Michael
T1  - Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: an international randomized phase III trial
T2  - Neuro-oncology
N2  - Background: Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in patients with glioblastoma (GBM), but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase III CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO) + RT compared with TMZ + RT in newly diagnosed GBM with unmethylated MGMT promoter.
Methods: Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) or RT + TMZ (75 mg/m2 daily during RT and 150–200 mg/m2/day 5/28 days during maintenance). The primary endpoint was OS.
Results: A total of 560 patients were randomized, 280 to each arm. Median OS (mOS) was 13.4 months (95% CI, 12.6 to 14.3) with NIVO + RT and 14.9 months (95% CI, 13.3 to 16.1) with TMZ + RT (hazard ratio [HR], 1.31; 95% CI, 1.09 to 1.58; P = .0037). Median progression-free survival was 6.0 months (95% CI, 5.7 to 6.2) with NIVO + RT and 6.2 months (95% CI, 5.9 to 6.7) with TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65). Response rates were 7.8% (9/116) with NIVO + RT and 7.2% (8/111) with TMZ + RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively.
Conclusions: The study did not meet the primary endpoint of improved OS; TMZ + RT demonstrated a longer mOS than NIVO + RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ + RT as the standard of care for GBM.
ClinicalTrials.gov NCT02617589
KW  - newly diagnosed glioblastoma
KW  - nivolumab
KW  - radiotherapy
KW  - temozolomide
KW  - unmethylated MGMT
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63310
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-633107
SN  - 1522-8517
N1  - The data sets presented in this  article are not readily available because requestors must complete a data request on the BMS investigator portal. Requests to access the data sets should be directed to https://fasttrack-bms.force.com/Login. Bristol Myers Squibb’s policy on data sharing may be found at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html.
N1  - Early View: Online Version before inclusion in an issue
VL  - 2022
IS  - art. noac099
SP  - 1
EP  - 12
PB  - Oxford Univ. Press
CY  - Oxford
ER  -