NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma.

Background: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older.
Methods: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm.
Results: A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events.
Conclusions: Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations.
Competing Interests: HWS acknowledges institutional research funding from AbbVie and Bristol-Myers Squibb and has received honoraria from Eli Lilly. ABH serves on the advisory board of Caris Life Sciences and WIRB-Copernicus Group, and is supported by research grants from AbbVie, Alnylam Pharmaceuticals and Cellularity. BME serves on the advisory board and as a consultant for Alpheus Medical, Curtana Pharmaceuticals, Ellipses Pharma, Global Coalition for Adaptive Research, ImmunoGenesis, Medicenna, MedQIA, Monteris, Neosoma, Sagimet Biosciences, Sapience Therapeutics, Servier Pharmaceuticals, Siemens and Sumitomo Pharma Oncology, serves as a consultant for Carthera and Chimerix, and is supported by a research grant from Siemens. HG serves on the advisory board of Merck Serono, and serves as a consultant for Curis and Telix Pharmaceuticals. HL acknowledges institutional research funding from Pfizer, and has received honoraria from AstraZeneca. JRS acknowledges institutional research funding from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Cancer Australia, Cancer Institute NSW, Merck Serono, National Health and Medical Research Council of Australia, Pfizer and Roche. ZL serves on the scientific advisory committee of Merck Sharp Dohme, has received honoraria from AstraZeneca, Bristol-Myers Squibb and Roche, and has received travel funding from Pfizer. MK acknowledges institutional research funding from AbbVie, Bristol-Myers Squibb and Specialized Therapeutics, and has received honoraria from AbbVie, Bristol-Myers Squibb, Eli Lilly, Ipsen, Pfizer and Roche.
(© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)