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Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter
- Source :
- Neuro-oncology, vol 24, iss 11
- Publication Year :
- 2022
-
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/m2 once daily during RT, then 150-200 mg/m2 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.
- Subjects :
- PD-L1
Cancer Research
Clinical Trials and Supportive Activities
Oncology and Carcinogenesis
610 Medicine & health
Antineoplastic Agents
temozolomide
MGMT promoter
Rare Diseases
Clinical Research
Adrenal Cortex Hormones
Genetics
Temozolomide
Humans
1306 Cancer Research
Oncology & Carcinogenesis
Antineoplastic Agents, Alkylating
DNA Modification Methylases
Cancer
nivolumab
Brain Neoplasms
Tumor Suppressor Proteins
glioblastoma
Neurosciences
Evaluation of treatments and therapeutic interventions
Chemoradiotherapy
Alkylating
10040 Clinic for Neurology
Brain Disorders
Brain Cancer
2728 Neurology (clinical)
Nivolumab
DNA Repair Enzymes
Oncology
6.1 Pharmaceuticals
2730 Oncology
Neurology (clinical)
Glioblastoma
Subjects
Details
- ISSN :
- 15235866
- Volume :
- 24
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Neuro-oncology
- Accession number :
- edsair.doi.dedup.....76d2a4d9a4a9461444c8f2e21dc2c19d