I was talking about microsatellite instability and its applications for treatment. In my talk I’ve explained to people what microsatellite instability is and how it’s a potentially key target that we can focus treatments on in gynaecological cancers. I think the key message for my talk is that microsatellite instability is common in endometrial cancer and that’s something that people aren’t always aware of. It occurs in about 25-30% of all endometrial cancer cases and for the majority of those cases it’s an acquired thing that can happen over time and it’s something that we need to test patients for at relapse. It’s also done as part of diagnosis because it is associated with a risk of a genetic syndrome called Lynch Syndrome, but for the majority of patients we’re talking about something that could be acquired and therefore when patients relapse it could be tested on in their cancers and it could have implications for treatment.

In endometrial cancer specifically it’s a huge area of unmet need. There is no standard of care for endometrial cancer beyond first line treatment so when patients relapse there are very limited treatment options. If, indeed, 25% of these women have microsatellite instability high levels then we could potentially look at targeting that. We’ve already got early phase trial data showing that immune checkpoint inhibitors such as pembrolizumab and TSR-042, which I also presented as part of my talk, show high levels of activity in these cancers. So this is data from early trials, small numbers of patients, but it’s a huge area of exploration for endometrial cancer and an opportunity obviously to treat patients where there are no standards of care. In the GARNET study , this was presented at AACR this year, there was a poster presentation and it showed nearly 50% of patients getting a partial response to treatment with single agent TSR-042. This is, as I say, in an area where there is no standard of care.

So these studies are very early, lots of data will come in larger numbers of patients but we need to be testing endometrial cancer patients for microsatellite instability. There are various ways in which that can be done but the first stage is for the national groups to put pressure on all of our institutions that this should be standard of care, that women should have access to this testing and that’s currently not the case.

Why is this?

NICE recommend testing in colorectal cancer patients so anyone with colorectal cancer can have a mismatch repair deficiency testing and microsatellite instability testing and it should be standard of care. This whole area in endometrial cancer has just probably not been thought about and considered whereas a lot of patients will present with endometrial cancer and then they won’t have the opportunity to have this test done. So we’ve got the ability to do it, so funding will be an issue, and it needs to probably come as a sort of national guidance that all women should have the testing. The ASCO guidelines support this in endometrial cancer, so it’s not just coming from the UK, it’s an international drive really.

Is the test the same across different cancer types?

It depends what you’re doing the test for. So if you’re doing the test to establish the risk of Lynch Syndrome, which is this genetic syndrome that’s associated with it, then probably you can do the same test regardless of cancer type. So you can probably do immuno-histochemical staining or you can do MSI/PCR testing. If you’re looking at treatment options and biomarkers for response to treatment then this may be done better through next generation sequencing panels where you’re looking at lots of different genes because obviously different cancer types might have different genetic abnormalities associated with this. So I think we can learn a lot from colorectal cancer but we can’t just extrapolate it all to gynae cancers. So we need to look at all of the data rather than just say we’ll copy the same thing.