German CLL8 - part 6

OK. So what about secondary endpoints? The important one for this trial is the difference in overall survival between chemotherapy and immunochemotherapy.

As you can see the curves are separating quite widely so that by 5 years follow-up of those who received FC 62% are still alive, whereas, of those who received FCR 75% are still alive. Unfortunately, there are very few patients who have been followed up for 5 years, so down at the right hand end of the graph the figures are not statistically significant - they could have occurred by chance. We are only going to see how big the difference between the two treatments as the trial matures. Indeed, if we go out even further, the lines actually cross, but the numbers are so small at this level, that the crossing is meaningless. The statisticians are only satisfied to report the position at a median of 3 years follow-up. Overall survival 3 years post randomization: FCR: 87.2% FC: 82.5% n=817, HR 0.664, p=0.012. These are the figures that Chris has been giving in his postings. It is a less than 5% difference, to be sure, but the point is that we are sure that it is a real difference, not one that could have happened by chance. Just by eyeballing the graph, we can be pretty sure that the difference will grow as time passes. But statisticians are creatures of exactitude and they won't allow us to say so until it is mathematically proven.

Let's just emphasize this point. For the first time with CLL a treatment has been shown to improve overall survival. Prior to this trial one could easily say that a treatment might give longer remissions, but if you are happy with less severe treatments given more frequently, then it doesn't matter which treatment you receive first. Three 12 month remissions are as good as two 18 month remissions. Now it is not possible to say that. If you go with FC rather than FCR as first line treatment then on average you waon't live as long.

Of course, patients want to know a great deal more than that. If for example you were absolutely sure that you would live longer with FCR than FC, but only 5 days longer, then I guess there wouldn't be many takers for a more aggressive treatment. So we do need to know some more details.

Here's one: The time to 25% of patients dying with FCR was 62.5 months, but with FC it was only 46.8 months. That is the quarter of patients who actually do worst with either of these regimes get an extra 15 months with FCR - and again that is statistically significant. So despite what Chris has been saying, this trial is holding out hope for improvement for a lot of people.