Any experience with targeted therapy for BRAF V600E mutated tumor(s)?

Posted by Tom Schwerdt @tomschwerdt, May 21, 2023

So, it seems a fair number of tumors are caused by a local mutation designated BRAF V600E. There are specific targeted therapies for cancers with this mutation which are FDA approved, usually dabrafenib combined with trametinib. I was wondering if anyone here had experienced this treatment approach or were aware of an oncologist comfortable with this approach.
https://en.wikipedia.org/wiki/V600E
- FDA grants accelerated approval to dabrafenib in combination with trametinib for unresectable or metastatic solid tumors with BRAF V600E mutation https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dabrafenib-combination-trametinib-unresectable-or-metastatic-solid

My own case is a bit more complicated since for some reason the medical community designates the tumor destroying my jawbone (mandibular ameloblastoma) as "not cancer". From the literature I've read, the majority (and likely the vast majority) of mandibular ameloblastoma cases have the BRAF V600E mutation.

Interested in more discussions like this? Go to the Cancer Support Group.

Colleen Young, Connect Director | @colleenyoung | May 30, 2023

I'm tagging @dgruk @duckduck2020 @audrapopp as they have experience with BRAF V600E mutated tumors.

@tomschwerdt, like others have mentioned, it seems odd that a growing tumor of abnormal cells is not categorized as cancer. Have you questioned this and received an explanation? I'd like to understand better.

Tom Schwerdt | @tomschwerdt | May 31, 2023

Hey @colleenyoung - I have not gotten a solid answer on that question. My original hypothesis was that ameloblastomas don't metastasize, but that was wrong. A small portion of ameloblastomas do metastasize.

Is there an oncologist who participates here that we could ping?

Had my initial surgery yesterday - early discussions called it a "biopsy" - but it was officially designated "removal for lesions" - likely to be weeks before lab results are in.

Tom Schwerdt | @tomschwerdt | Jun 15, 2023

Initial results are in after the initial pathologist sent it to a specialty pathologist - yes, ameloblastoma.

Unfortunately, the specialty pathologist didn't specify the subtype - my oral surgeon is after him to get more detailed.

For those interested in a simple chart of the subtypes: https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z/figures/1

Tom Schwerdt | @tomschwerdt | Sep 27 11:30pm

Hello all!

I've been participating in the Ameloblastoma thread in the Head and Neck group since May 2023. Ameloblastoma is extremely rare. Short version: Tumor grows inside bone in the mouth region, most often the mandible (jawbone.) Conventional treatment is either conservative (jaw preservation) surgery, or more radical surgery which generally has significant morbidity but reduces (not eliminates) the chances of recurrence. It's a sneaky tumor. Because it is so rare, it does not get much attention.

After going the conservative surgery route in 2007, I had the ameloblastoma come back ~15 years later. I dug into the medical literature again (PubMed) and found that a mandibular (jawbone) ameloblastoma has an ~80% likelihood of having the BRAF V600E mutation. And there are now FDA approved, targeted drug treatments for BRAF V600E.

There are very few studies on targeted BRAF therapy specifically for ameloblastoma (FDA approval was based on other cancers.) All the ameloblastoma studies are tiny, the largest being 11 patients, second largest being 3. Heck, when I brought the 11 patient study to MD Anderson, it wasn't even formally published yet. I found the information from preliminary results presented at a conference.

Anyway: Results in the studies are great. Virtually every patient shows tumor shrinkage/bone regrowth. It took some doing to get started on targeted therapy, but I did. I'm told I was the first person at MD Anderson to get targeted BRAF therapy for ameloblastoma.

Fortunately, targeted therapy is working well for me, if slower than I would like. Ongoing regrowth shown in the CT, including the followup a few weeks ago.

October 8th will be 1 year on the Mekinist + Taflinar (dabrafenib + trametinib) and we're far into uncharted territory. None of the studies have BRAF treatment even half as long. I believe I am the world record holder for longest targeted BRAF treatment of an ameloblastoma. Not something I ever aspired to, and I would LOVE for you to prove me wrong.

Many of the ameloblastoma patients in the targeted BRAF treatment studies were eventually given conservative surgery. Some had complete remission and just ended the BRAF therapy and went home. All of the studies are too recent for any long-term followup.

I just really don't know where things are likely to go from here. My original oncologist has left MD Anderson to head up a new cancer clinic. I have been assigned to a new oncologist, but I won't meet them for a month.

I am very interested in hearing from anyone who has been on BRAF V600E targeted treatment for their cancer. How long were you on it? Are you still on it? How well did it perform? What were your side effects? Did you try any additional therapies (surgery, conventional chemo, radiation, etc)? What else should I know?

Thank you.

-Tom