TAS-102 is a new drug, particular for Egypt it’s just recently approved. It’s available around the world and has been approved many years ago and showed very promising effect. In fact, the registration trial called RECOURSE showed significant improvement in progression free and overall survival which gives us one additional tool in the treatment of patients with metastatic disease so we don’t have only the multikinase inhibitor we have TAS-102. TAS-102 has a unique mechanism of action because it actually leads to double stranded DNA breakage, which is one of the few drugs which can do that. This is very important because the side effect profile of TAS-102 compared to Stivarga is completely different. Here the dose limited side effects are neutropenia. Usually oncologists are very worried about neutropenia; in the case of TAS-102 it’s very good news because patients who have neutropenia have a significantly longer progression free and overall survival. Even the patients where treatment has to be delayed, these are the patients who benefit the most. The reason is easy, because you have the incorporation of DNA of the trifluridine not only in tumour cells but also in white cells. So when it works in white cells it should more likely work in the tumour cells. So it’s a side effect we know how to deal with but it’s a very good predictive marker for the benefit of this drug in this patient population.
One of the challenges for clinicians is should I use Stivarga, a multikinase inhibitor, should I use TAS-102 which is now available? Efficacy-wise they are very similar, the toxicities are different with Stivarga more hand and foot disease and fatigue, here you have more haematological side effects such as neutropenia. So it depends on the overall performance of the patient, the previous treatment, comorbidities, what you think is the most effective treatment for your patient in front of you.
What’s the next step for this research?
I think the future right now is in addition to the new drug development, particularly for the microinstable, to identify more and more targetable mutations or genetic alterations, that is ongoing. So I’m sure I’m very optimistic we’ll find more and more which we will have a very effective treatment. There will be not a marker for everyone, there will be some markers for some which makes a big difference. With the development of Stivarga and the development of TAS-102 the next step is finding more successful combinations. So for TAS-102 because of this mechanism it could be PARP inhibitor, it could be patient selection who have a deficiency in DNA repair and for Stivarga a combination with immunotherapy. So both will evolve in combination and improve the efficacy of their mode of action.
How much do we consider quality of life in this setting?
Quality of life does not matter when we want to cure. When we have a patient in front of us which we can cure with a curative resection, toxicities are not a limiting factor. In later lines of treatment quality of life is very important, that is the reason the differences in toxicity profile between the available drugs are very important before you make the decision how to move forward. If somebody has already very low haemoglobin or has a hard time with neutropenia, TAS-102 would be not a good factor. If somebody is very fatigued and already in a bad performance status maybe that’s not a good patient for Stivarga. But this needs to be discussed and evaluated on an individual basis.
