Antonio Omuro, Alba Brandes, Antoine Carpentier, Ahmed Idbaih, David A. Reardon, Timothy Cloughesy, Ashley Sumrall, Joachim Bähring, Martin J. Van den Bent, Roy Oliver Bähr, Giuseppe Lombardi, Paul Mulholland, Ghazaleh Tabatabai, Ulrik Lassen, Juan Manuel Sepúlveda, Mustafa Khasraw, Elodie Vauleon, Yoshihiro Muragaki, Anna Maria Di Giacomo, Nicholas Butowski, Patrick Roth, Xiaozhong Qian, Alex Z. Fu, Yanfang Liu, Von Potter, Alexandros-Georgios Chalamandaris, Kay Tatsuoka, Michael Lim, Michael Weller
- 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
MetadatenAuthor: | Antonio OmuroORCiD, Alba BrandesORCiDGND, Antoine CarpentierORCiD, Ahmed IdbaihORCiD, David A. ReardonGND, Timothy CloughesyORCiDGND, Ashley SumrallORCiD, Joachim BähringGND, Martin J. Van den BentORCiDGND, Roy Oliver BährGND, Giuseppe LombardiORCiD, Paul MulhollandORCiD, Ghazaleh TabatabaiORCiDGND, Ulrik LassenORCiD, Juan Manuel SepúlvedaORCiD, Mustafa KhasrawORCiD, Elodie VauleonORCiD, Yoshihiro MuragakiORCiD, Anna Maria Di GiacomoORCiD, Nicholas Butowski, Patrick RothGND, Xiaozhong Qian, Alex Z. FuORCiD, Yanfang Liu, Von Potter, Alexandros-Georgios ChalamandarisORCiD, Kay Tatsuoka, Michael LimGND, Michael WellerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-633107 |
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DOI: | https://doi.org/10.1093/neuonc/noac099 |
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ISSN: | 1522-8517 |
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Parent Title (English): | Neuro-oncology |
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Publisher: | Oxford Univ. Press |
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Place of publication: | Oxford |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2022/04/14 |
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Date of first Publication: | 2022/04/14 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2022/11/28 |
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Tag: | newly diagnosed glioblastoma; nivolumab; radiotherapy; temozolomide; unmethylated MGMT |
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Volume: | 2022 |
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Issue: | art. noac099 |
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Article Number: | noac099 |
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Page Number: | 12 |
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First Page: | 1 |
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Last Page: | 12 |
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Note: | 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. |
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Note: | Early View: Online Version before inclusion in an issue |
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HeBIS-PPN: | 507181999 |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International |
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