We have now approved medications in third line and beyond, one of them is regorafenib, it’s a multikinase inhibitor. The interesting mechanism of action is that it detects not only the angiogenesis but also the immune pathways, the tumour growth and the metastatic potential. So it targets very critical pathways which are responsible for tumour growth and progression. The interesting new finding for regorafenib is that it really impacts immune response pathways. We know it inhibits CSF-1 which is one of the receptors which is responsible for attracting tumour associated macrophages. These are the bad ones, facilitating tumour growth. When you inhibit these macrophages actually the chemotherapy or the multikinase inhibitor will be more effective. But not only that, now because of this mechanism combinations of regorafenib and immune checkpoints are ongoing to really take advantage of this potential synergism. So regorafenib has shown in many thousands of patients to have a consistent effect, increasing progression free survival, increasing overall survival so we have a very valuable option for patients in third line treatment.

We also have learned to use the drug better. In the beginning we started with the standard dose, we now have learned in a recent publication that when we start with 80mg increasing to 120mg after one week and then to 160mg, if no toxicities, we not only maintain the efficacy we increase the efficacy by decreasing toxicity. That’s a very important step, how to manage this patient in the future even better than we do today.

Are these inhibitors being used currently?

Regorafenib is approved basically around the world, in Egypt for a couple of years, so they have been readily used everywhere.

Is there any research on new inhibitors or other targets?

There are a lot of new drug developments going on with new targets. The major focus in colorectal cancer is looking at the role of immuno-combinations in microsatellite stable tumours. There are more than a thousand trials going on in the world, no-one knows how to find successful combinations to convert a cold tumour to an immunological hot tumour. So the verdict is out, hopefully we’ll find some promising new combinations.