Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Issue 11 (2nd May 2022)

• Record Type: Journal Article
• Authors: Lim, Michael; Weller, Michael; Idbaih, Ahmed; Steinbach, Joachim; Finocchiaro, Gaetano; Raval, Raju R; Ansstas, George; Baehring, Joachim; Taylor, Jennie W; Honnorat, Jerome; Petrecca, Kevin; De Vos, Filip; Wick, Antje; Sumrall, Ashley; Sahebjam, Solmaz; Mellinghoff, Ingo K; Kinoshita, Masashi; Roberts, Mustimbo; Slepetis, Ruta; Warad, Deepti; Leung, David; Lee, Michelle; Reardon, David A; Omuro, Antonio
• Is Part Of: Neuro-oncology. Volume 24:Issue 11(2022)
• Page Start: 1935
• Page End: 1949
• Publication Date: 2022-05-02
• Subjects: glioblastoma -- MGMT promoter -- nivolumab -- PD-L1 -- temozolomide; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac116
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III 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 [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m 2 once daily during RT, then 150-200 mg/m 2 once daily on 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.