V600E

There's no Siglin D1.

There's no BRAF V600E.

There's no translocation 1418 with BCL2.

There's nothing you can point at and say, yes, there, that's the one.

But I mean, me sort of hedging here does mean that a mid-88 negative lymphoplasmic acidic lymphoma exists and a mid-88 positive marginal zone lymphoma exists.

And as a brief name drop for the hairy cell leukemia series, which will probably get a bonus episode or series, who knows, can also present with splenomegaly and cytopenias and these villous-ish cells.

But hairy cell is distinguished because it's 11C bright, 25, 103, 123, and X and A1 positive, and BRAF V600E mutated in essentially all cases.

It generally phenotypes out pretty cleanly.

So I, um, want to share my experience with a patient that was diagnosed in April twenty twenty-two with stage four non-small cell lung cancer with an adenocarcinoma.

Uh, PD-L1 tested positive thirty percent, uh, and she tested negative for, uh, EGFR mutations, ALK, ROS, uh, fusions, BRAF V600 mutations, and HER2 mutations.

And the patient was subsequently treated with carboplatin, pemetrexed, and pembrolizumab, uh, in the period from May twenty twenty-two to October twenty twenty-four, and the best response was p- a partial response.

You can see here the scan that was, uh, uh, this, um, chest X-ray that was made in April twenty twenty-two.

Other mutations include NTRK mutations, which are rare but actionable with TRK inhibitors.

BRAF V600E and RET mutations are also rare but targetable.

And then, of course, we have our RAS mutation as well, which we talked about.

I think the biggest take-home from all of this, though, is just remember, germline testing and somatic profile testing early is really, really important.

Um, for example, um, one of our cancer panels can't do, um, uh, copy number alterations.

So we can find DNA alterations, um, and so for example, like BRAF V600E, which is very, very easy to find, IDH1, IDH2.

Um, but amplifications or copy number losses of specific, um, genes is... can be a little bit trickier.

So I would say for the interpretation, um, it's very challenging for community-based and for people who aren't thinking about this on a daily basis to understand what the results are telling them, as well as, um, what might be missing in that particular testing.

So initially, the initial readout was the phase three cohort three randomized open label trial.

First line BRAF V600E mutant MCRC with either local tissue or blood or central testing as well.

The initial readout was randomizing patients to Fofox EC versus investigator's choice chemotherapy, basically.

And there you saw an initial improvement in response rates, which was the primary endpoint.

I think I'm not opposed to start higher dose of iron ore taken in the U.S. population because of historically more challenges with the high dose of 5FU.

Great takeaways.

I'll ask both of you one last question on this topic of BRAF V600E mutant.

Often coexists with MSI high status.