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Re: Lykiri post# 526202

Monday, 10/31/2022 1:10:30 PM

Monday, October 31, 2022 1:10:30 PM

Post# of 700693
Lykiri, I have 2 reasons to think the majority of the 35 non-crossover placebo patients are MGMT methylated.

The first one is as follows:

From the JTM publication we know the following:



From the NYAS we know the following for the nGBM arm:



And the following for the rGBM arm:



With this, we know that the percentage of patients with unknown MGMT methylation decreased between JTM and NYAS from 11.48% to 4.74% for the case of the nGBM arm and to 4.69% for the case of rGBM arm. Actually very similar percentages of 4.7% for nGBM and rGBM arms.

So I think it is accurate to assume that 4.715% (average between 4.74% and 4.69%) of the patients in the group of 35 remaining patients have unknown MGMT methylation. This equals to 2 patients (35 * 4.715% = 1.65).

With this, we can estimate a total of 16 unknown MGMT methylation in the whole trial (11 from nGBM arm, 3 from rGBM arm and 2 from the other group of 35 patients).

As a consequence of this, we have 22 patients (38 - 16) that had unknown MGMT methylation in the JTM journal publication and were then identified as MGMT Methylated or MGMT unmethylated.

In order to distribute these 22 patients between MGMT Methylated and MGMT unmethylated, what I did was to use the proportion of 131 MGMT methylated patients and 162 MGMT unmethylated patients from the JTM jourmal publication. With this, I obtained a distribution of 10 methylated and 12 unmethylated.

After adding the 10 methylated and the 12 unmethylated patients to the JTM numbers I obtained the following:



With this we obtain the following numbers for the 35 reamining patients by substracting the numbers in the tables corresponding to NYAS nGBM and rGBM arms from the numbers in the table above :



The second reason is that for me it makes sense that the patients that evented are more likely to be MGMT unmethylated than MGMT methylated, so I expect more methylated remaining in the group of 35.
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