Ann: Positive New HER-Vaxx HERIZON Data Presented at ESMO Asia, page-56

Hi Cuixot

Your original question was not "silly" when you asked "does anyone know what 'Patients @ Risk means' as used in the ESMO presentation ??"

I believe you are correct. "Patients At Risk" is the count of patients who are still in the study and therefore considered "at risk" of the event which is being measured/monitored. In the Her-vaxx study that "event" is death.

So, at first glance the "Number of Patients at Risk" count starts at 19 (for the Her-vaxx + Chemo cohort) and it ends at zero - which makes it look as though all 19 patients have died.

However as you point out the chart includes a key which states that a cross mark indicates "Censor." The last 3 horizontal lines contain a total of 4 such cross marks, indicating that 4 patients have indeed been "Censored."

What does "Censored" mean in this context? The best explanation I can find is: "Censoring means the total survival time for that subject cannot be accurately determined. This can happen when something negative for the study occurs, such as the subject drops out, is lost to follow-up, or required data is not available or, conversely, something good happens, such as the study ends before the subject had the event of interest occur, i.e., they survived at least until the end of the study, but there is no knowledge of what happened thereafter. Thus censoring can occur within the study or terminally at the end."

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932959/

The same source includes this very useful comment:

"It helps to understand this further if we remember that clinically we may get information on our patients indefinitely; however, research is expensive, has a beginning and an end, and is formally closed when the study is complete (figuratively the lights go off, the telephones are not answered, and files are stored, and everyone goes to another job)."

So it looks to me as though - yes - four out of the 19 Her-vaxx plus Chemo patients may still be alive. We just do not know for sure, based on the info at hand, because I cannot see anything which states specifically when the study follow up ended. ie. when the lights went off, the phones stopped being answered, the files were stored and everyone nicked off to the pub.

Looking at the chart in the presentation, the last recorded "event" was at just over 21 months, so my best guess is that the study ended at that point. You may recall LC telling everyone in an interview that they needed to wait for a certain number/proportion of "events" before they could process OS data. In fact the Company Ann of 1 Sept last year stated that "Imugene is awaiting the events needed for OS evaluation and will subsequently analyse all data". (A polite way of saying that they were waiting for enough patients to die).

If I am correct in this, then you will see that two patients were "Censored" ie dropped out before the study ended. One dropped out at around 16.5 months and the other at 21 months. The other two are just recorded as "Censored" on the long final tail of the chart which I think is after the study officially ended - which I interpret as meaning that they were still alive when the study ended.

We have no way of knowing if any of or all of the 4 censored patients are still alive, but given the dismal medical condition required for inclusion in the study they certainly beat the odds to get to the point where they dropped off the study radar.

To put this in some perspective, we are all of us "at risk" of the same event. In fact on a long enough time frame we are all certain to reach that final "event." Most of us are not being formally studied for our own OS data and most of us try not to think about it too much, but we should all spare a thought for the poor people who are living with cancer, or other life threatening illness, and we should all do what we can to ensure that the remaining minutes/days/weeks/months/years we ourselves may have are well spent - enjoying what we are fortunate to have, helping others who need our help, and giving and accepting love in all its many forms.

Best wishes

Dave