CheckMate 548 & CheckMate 143 & CheckMate 498
CheckMate 548, 143 and 498 were three large trials, all negative: the immunotherapy that transformed melanoma and lung cancer did nothing in glioblastoma.
CheckMate 143 (recurrent, n=369): OS 9.8 vs 10.0 months with bevacizumab. CheckMate 498 (unmethylated, nivolumab replacing temozolomide): OS 13.4 vs 14.9 months, worse. CheckMate 548 (methylated, nivolumab added): no PFS or OS benefit. 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.
- Median 28.9 vs 32.1 months with Nivolumab + RT + temozolomide compared with Placebo + RT + temozolomide; about 3.2 months shorter for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 10 percent higher chance of the event at any given time (hazard ratio 1.1, likely range 0.92 to 1.32).
- The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Glioblastoma: nivolumab added to standard therapy (newly diagnosed, MGMT-methylated CM548; MGMT-unmethylated vs temozolomide CM498) and nivolumab vs bevacizumab at recurrence (CM143). People in a different situation may not see the same effect.
- The trial selected people by a biomarker (MGMT); the result should not be assumed for people whose cancer does not have it.
- Not significant.
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 participants 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 (0.92–1.32) | — | link |
| Placebo + RT + temozolomide | 358 | 32.1 months |
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