NOA-08
NOA-08 showed that older people with glioblastoma can be treated with temozolomide tablets instead of six weeks of radiotherapy without living less long, and that the MGMT test tells you which to choose: chemotherapy if the gene is methylated, radiotherapy if it is not.
Overview
NOA-08 (Methusalem) was a randomised phase 3 non-inferiority trial of the German Neuro-oncology Working Group in 412 patients over 65 with anaplastic astrocytoma or glioblastoma. Patients received dose-dense temozolomide 100 mg/m2 one week on, one week off, or radiotherapy of 60 Gy; 373 were treated and analysed. The primary endpoint was overall survival.
Median overall survival was 8.6 months with temozolomide and 9.6 months with radiotherapy (hazard ratio 1.09), meeting the non-inferiority margin, and event-free survival did not differ. MGMT promoter methylation predicted longer survival overall and, critically, predicted which treatment worked: event-free survival was 8.4 months with temozolomide against 4.6 with radiotherapy in methylated tumours, and 3.3 against 4.6 months in unmethylated tumours. With the Nordic trial, NOA-08 is why the corpus's glioblastoma page chooses between temozolomide alone and radiotherapy alone by MGMT status in older patients.
- Median 8.6 vs 9.6 months with Dose-dense temozolomide alone compared with Radiotherapy alone (60 Gy); about 1 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 9 percent higher chance of the event at any given time (hazard ratio 1.09, likely range 0.84 to 1.42).
- 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.
- Median 3.3 vs 4.7 months with Dose-dense temozolomide alone compared with Radiotherapy alone (60 Gy); about 1.4 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 15 percent higher chance of the event at any given time (hazard ratio 1.15, likely range 0.92 to 1.43).
- The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- Median 8.4 vs 4.6 months with Dose-dense temozolomide alone compared with Radiotherapy alone (60 Gy); about 3.8 months longer 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.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- Median 3.3 vs 4.6 months with Dose-dense temozolomide alone compared with Radiotherapy alone (60 Gy); about 1.3 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.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- Median 11.9 vs 8.2 months with MGMT promoter methylated compared with MGMT promoter unmethylated; about 3.7 months longer 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 38 percent lower chance of the event at any given time (hazard ratio 0.62, likely range 0.42 to 0.91).
- 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: Patients over 65 with newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky score of 60 or more: dose-dense temozolomide (one week on, one week off) alone against radiotherapy alone (60 Gy), with overall survival non-inferiority as the primary endpoint and MGMT promoter methylation analysed. 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.
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.
412 enrolled.
95% CI 7.3 to 10.2 · 95% CI 8.2 to 10.8
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (non-inferiority)primary | Dose-dense temozolomide alone | 195 | 8.6 months | 1.09 (0.84 to 1.42) | 0.033 (non-inferiority) | link |
| Radiotherapy alone (60 Gy) | 178 | 9.6 months | ||||
| Event-free survival | Dose-dense temozolomide alone | 195 | 3.3 months | 1.15 (0.92 to 1.43) | 0.043 (non-inferiority) | link |
| Radiotherapy alone (60 Gy) | 178 | 4.7 months | ||||
| Event-free survival, MGMT promoter methylated | Dose-dense temozolomide alone | - | 8.4 months | - | - | link |
| Radiotherapy alone (60 Gy) | - | 4.6 months | ||||
| Event-free survival, MGMT promoter unmethylated | Dose-dense temozolomide alone | - | 3.3 months | - | - | link |
| Radiotherapy alone (60 Gy) | - | 4.6 months | ||||
| Overall survival by MGMT status (both arms) | MGMT promoter methylated | - | 11.9 months | 0.62 (0.42 to 0.91) | 0.014 | link |
| MGMT promoter unmethylated | - | 8.2 months |
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