I sometimes get asked by fellow Stage IV patients questions on the science of clinical trial possibilities. The very first question I always ask back is “Do you know if you are MSI-high or MSS?”.
I ask this because of the ASCO-2015 presentation and New England Journal of Medicine (NEJM) article (here: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1500596
) which show a very significant effect of this “MSI biomarker” on response to the hottest current immunotherapy drug class, “PD-1 inhibitors”, in this case the drug “pembrolizumab (Keytruda)”. Scientifically it makes a lot of sense that MSI-high would be more likely to respond to this class of drugs. It was great to see this shown in preliminary trial data, I think there is a high chance that it will be confirmed in larger trials. There are multiple PD-1 (and closely related PD-L1) inhibitors in clinical trials. In other cancer types, the various inhibitors of this class have shown relatively similar efficacy profiles so far, although this remains to be seen in published MSI-CRC trials.
PD-1 inhibition in other cancer types has generated very long term remissions and stable disease (years!) in some patients. Although it remains to be seen if this will be the case in MSI-CRC, the very plausible scientific possibility of this happening makes exploring the possibility of a PD-1 inhibitor therapy a very important discussion to have with your MD if you are MSI-high. If you don’t know if you are… by the same sentiment, it makes finding out your MSI-status a key goal. I recommend printing out the above NEJM paper to discuss with your MD getting the test done. It is a test your MD can order if tissue sample is available.
If you are MSI-high, the strategic timing of when to switch to some sort of anti-PD-1 therapy is a decision you individually need to make with your MD. There is a chance that taking a PD-1 inhibitor now may preclude you from future combination clinical trials. There are currently multiple clinical trials open. I also personally know a MSI-CRC patient who was not able to travel to a trial but she is getting a PD-1 inhibitor right now from the drug company via “compassionate use”.
I suggested to put your MSI-status in your signature line as an easy reminder to find out the data if you don’t know the answer yet… I'll update mine today
As I posted in May – I personally believe this is the highest impact new therapy to hit CRC in many years. I personally know multiple MSI-high patients responding to it.
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/2016 Colondar 2.0 ModelDK37 Science Posts List