Det har vært litt spm og prat her om PFS og OS (bl.a om hvorfor man ikke alltid velger OS, og om ikke PFS alltid vil være en klare indikasjon på hva også OS vil vise senere).
Jens sa litt om dette på Q4 for et halvt år siden og eksempelet hans var hva som skjedde med registreringstudien (CM743) som ledet til godkjenning av ipi+nivo for nettopp mesothelioma – dvs.i samme kreftform som NIPU-studien :
But back to the endpoints on progression-free survival versus overall survival. So if we look at the next slide here. For all patients with cancer, of course, the gold standard and also for the medical community – overall survival is the gold standard. So you want to help the patients, so they survive their cancer.
In some indications, and if you treat in an early line, it will be in some indications several years until patients eventually die from the disease. To be in a position where we can do clinical trials that have – goes over a relevant number of years, not take too long, so-called surrogate endpoints are developed. And one of these endpoints, are PFS.
So for – when you develop the drug, it’s important to understand how the PFS, for example, associates or correlates with the overall survival in the end. We have an example of that here to the right. In the upper part of this figure, you can see the progression-free survival of the control arm in the red and the intervention arm in blue from the registration study of ipilimumab and nivolumab in mesothelioma.
So the red line represents chemotherapy, which was the control arm and standard of care for these patients at the time study was conducted, and the blue arm represents the patients that received nivolumab and ipilimumab.
If you look at the I-axis in the upper part of this figure at 50% and make a line – take a line horizontally out there, you will see that 50%, which represents the median PFS. The median PFS was better with chemotherapy as compared with ipi and nivolumab.
And thereafter, if you go to the lower part of this figure, you can see that here in the overall survival readout, the CPIs, ipilimumab and nivolumab actually had a better overall survival than the chemotherapy group. So if you select a trial and your final endpoint was progression-free survival only and you conclude on that without having additional secondary endpoint information to look at, you might conclude that the upper part of the study or upper picture here concludes that the study is a negative one.
But if you look further to overall survival, in this case, was also an endpoint in this study, you can see that there is actually an overall survival benefit in this study. So it’s important to understand the association between surrogate endpoints and overall survival in the end.
