We are unclear whether it should be given in the frontline setting. The patients may benefit more if they receive cytoreduction with chemotherapy first and then go on to one of those agents. Do you use them with chemotherapy? Do you use them as a second-line agent? Where do they fit in the world of adjuvant therapy? All those are interesting questions and we hope we are going to move the field forward for our patients.
Is there thought of bringing immunotherapy into patients with microsatellite-stable CRC?
There are trials that are looking at how we can combine checkpoint inhibitors, specifically PD-1/PD-L1 agents to perhaps sensitize them to an immuno-oncology drug. Or, can you give MEK inhibitors with chemotherapy? Can you sequence them after chemotherapy as a form of maintenance therapy? Many of these concepts hold a lot of water, but we do not have much clinical data to show where they are best used.
What do the next 5 years of this treatment landscape look like?
We are still badly in need of refractory agents. Hopefully, we will start to see something that adds to patients’ options once they progress through standard first- and second-line therapies. We know there are some patients who do badly. It appears that BRAF V600E mutations have a very aggressive phenotype and do not do very well. We need to add to what we can provide for that subgroup of patients and further refine what the role of PD-1/PD-L1 immuno-oncology agents are.