Phase 3 Trial of Chemoradiotherapy With Temozolomide Plus Nivolumab or Placebo for Newly Diagnosed Glioblastoma With Methylated MGMT Promoter. Neuro-oncology Lim, M., Weller, M., Idbaih, A., Steinbach, J., Finocchiaro, G., Raval, R. R., Ansstas, G., Baehring, J., Taylor, J. W., Honnorat, J., Petrecca, K., De Vos, F., Wick, A., Sumrall, A., Sahebjam, S., Mellinghoff, I. K., Kinoshita, M., Roberts, M., Slepetis, R., Warad, D., Leung, D., Lee, M., Reardon, D. A., Omuro, A. 2022


BACKGROUND: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase 3 randomized CheckMate 548 study was to evaluate RT+TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587).METHODS: Patients (N=716) were randomized 1:1 to NIVO [(240mg every 2 weeks *8, then 480mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75mg/m 2 once daily during RT, then 150-200mg/m 2 once daily days 1-5 of every 28-day cycle *6)] or PBO+RT+TMZ following the same regimen. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients without baseline corticosteroids and in all randomized patients.RESULTS: As of December 22, 2020, median (m)PFS (blinded independent central review) was 10.6 months (95% CI, 8.9-11.8) with NIVO+RT+TMZ vs 10.3 months (95% CI, 9.7-12.5) with PBO+RT+TMZ (HR, 1.1; 95% CI, 0.9-1.3) and mOS was 28.9 months (95% CI, 24.4-31.6) vs 32.1 months (95% CI, 29.4-33.8), respectively (HR, 1.1; 95% CI, 0.9-1.3). In patients without baseline corticosteroids, mOS was 31.3 months (95% CI, 28.6-34.8) with NIVO+RT+TMZ vs 33.0 months (95% CI, 31.0-35.1) with PBO+RT+TMZ (HR, 1.1; 95% CI, 0.9-1.4). Grade 3/4 treatment-related adverse event rates were 52.4% vs 33.6%, respectively.CONCLUSIONS: NIVO added to RT+TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter. No new safety signals were observed.

View details for DOI 10.1093/neuonc/noac116

View details for PubMedID 35511454