Great question, tough topic, we have a few patients who have had varient mutations and when they failed immunotherapies we have utilized either a braf or a mek inhibitor to try and slow or arrest their disease. The inhibition is not as robust as with a true BRAF V600 E, K or M variant but the pt may receive some term of benefit. Approval of inhibotors for variant mutations, can either go smoothly or a letter of medical necessity may be required with a peer reviewed journal article &/ or a peer to peer may also be necessary.
We’ve gone the clinical trial route for a lot of these patients – I agree that responses typically aren’t as robust, if there is even a response. But, I do have one exception – he’s been on BRAF therapy for 6 years! Crazy!
Such a great question.
to add onto this conversation thread…
Not only have we seen many non-target mutations in known target-able genes such as BRAF, but also with some of the broader spectrum molecular panels available (either commercially or institution based) we are identifying a lot of mutations that we can’t necessarily target right now, outside of a clinical trial.