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CheckMate 548 added nivolumab to standard radiotherapy and temozolomide in newly diagnosed glioblastoma and found no benefit. With CheckMate 143 and 498 it makes three large negative trials: the immunotherapy that transformed melanoma and lung cancer did nothing in glioblastoma.
CheckMate 548, trial NCT02667587 sponsored by BMS, randomised 716 patients with newly diagnosed glioblastoma and a methylated MGMT promoter to nivolumab or placebo added to radiotherapy and temozolomide. Median progression-free survival by blinded central review was 10.6 versus 10.3 months and median overall survival 28.9 versus 32.1 months (HR 1.1, 95% CI 0.9-1.3 for both); grade 3/4 treatment-related adverse events were more frequent with nivolumab (52.4% versus 33.6%). Published by Lim and colleagues in Neuro-Oncology (2022;24:1935-1949). Together with CheckMate 143 (recurrent) and CheckMate 498 (MGMT-unmethylated) it completes three negative phase 3 trials of PD-1 blockade in glioblastoma. Explanations: low mutational burden, T-cell exclusion behind the blood-brain barrier, steroid immunosuppression, systemic lymphopenia. Neoadjuvant PD-1 (Cloughesy 2019) showed immune activation and remains the only encouraging signal.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
716 enrolled.
Not significant
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival, MGMT-methylated glioblastomaprimary | Nivolumab + RT + temozolomide | 358 | 28.9 months | 1.1 (0.92 to 1.32) | - | link |
| Placebo + RT + temozolomide | 358 | 32.1 months |
Shares Neoadjuvant immunotherapy with surgical window for glioblastoma, MGMT promoter methylation, Blood-brain barrier (BBB), Hot vs cold tumours.
Shares Neoadjuvant immunotherapy with surgical window for glioblastoma, Blood-brain barrier (BBB), Hot vs cold tumours, Nivolumab.
Shares MGMT promoter methylation, Temozolomide, Glioma & glioblastoma.
Shares MGMT promoter methylation, The brain: barrier and sanctuary, Temozolomide, Glioma & glioblastoma.
Shares Blood-brain barrier (BBB), The brain: barrier and sanctuary, Glioma & glioblastoma.
Shares Blood-brain barrier (BBB), The brain: barrier and sanctuary, Glioma & glioblastoma.
Shares MGMT promoter methylation, Temozolomide, Glioma & glioblastoma, IMRT / IGRT (modern external beam).
Shares Blood-brain barrier (BBB), The brain: barrier and sanctuary, Glioma & glioblastoma.