Wednesday, June 27, 2018
Well, okie dokie!!! BRAFTOVI/MEKTOVI (Seriously guys??? That's the name???!!!) Encorafenib with Binimetinib approved for melanoma.
Here's a link to the nice little ad (I mean announcement!!!): ARRAY pharma gains FDA approval for the Encorafenib/Binimetinib
Here are prior posts on the combo:
This from May 2017: Encorafenib/binimetinib, a BRAF/MEK combo = 14.9 month PFS
PFS of 14.9 months is better than 12. Wish they had allowed testing in a greater swath of patients. (But I say that about most all trials!!!) We'll have to see what the OS data shows and if these current figures hold in future cohorts.
This from March 2018: Encorafenib plus binimetinib better than vemurafenib or encorafenib alone in melanoma! Well, duh!!! We already knew that a BRAF/MEK combo is better than a single agent!!!
Here are some snippets from that post:
I report this again only because "they" are! Institutions, Big Pharma, and researchers like to have their name in lights. So, I will shine my spotlight once again! I reported on and evaluated the results of the COLUMBUS study here, back in May of 2017: Encorafenib/binimetinib, a BRAF/MEK combo = 14.9 month PFS
Now that title statement, is absolutely true and good!!! In that report, I went to the trouble to look up these stats:
From The coBRIM trial - August 2016 we learned - that when cobinmetinib and vemurafinib were combined, the median overall survival (OS) was 22.3 months and the median progression free survival (PFS) was 12.3 months.
From this discussion of BRAF/MEK and immunotherapy (Nov 2016) we learned = that generally treatment that was a combination of a BRAF inhibitor and a MEK inhibitor could illicit a response rate of 48-59%, even as much as 70% with some combo's and PFS of 11-12 months.
So, yes...the encorafenib with vemurafenib combo has a better PFS than the combo's noted above ~ at least in this study of the 192 BRAF positive unresectable/metastatic Stage IIIB/C or Stage IV peeps who were given it below.....
[The abstract followed (you can see it for yourself via the link above).] My synopsis:
But... Here are some comments I made (in red) in the prior post which provides more info about the trial and trial results than this re-run abstract just posted in the Lancet:
Those with untreated CNS lesions, leptomeningeal metastases, uveal melanoma, and mucosal melanoma were excluded from the trial. [Why the hell not???? You could put them in their own separate group, so as not to sully your results Array CEO person!!! And still give them access to the drug!]
In Part 1 of the study, the median PFS was 14.9 months with the combination of encorafenib and binimetinib compared with 7.3 months for vemurafenib alone. The improvement in PFS represented a 46% reduction in the risk of progression or death. [That's good, but of course we have learned never to give vemurafenib, a BRAF inhibitor without a MEK inhibitor!!! So that's a bit of a false comparison!]
The objective response rate (ORR) with the combination was 63%versus 40% with vemurafenib. [Again...not comparing apples to apples...we KNOW that response rates are better with a BRAF/MEK combo!!!] With single-agent encorafenib, the ORR was 51%. [This fact can at least be compared to single agent vemurafenib response rate of 40%.]
Grade 3/4 AEs were experienced by 58% of patients treated with the combination versus 66% and 63% with encorafenib and vemurafenib, respectively. [As previously demonstrated, side effects were DECREASED with a BRAF/MEK combo.]
Okay. My synopsis is this: Generally, prior studies of BRAF/MEK combos demonstrate about a 12 month PFS. This combo showed a PFS of 14.9 months. Objective response rate was 63% with the comb0. There was an ORR of 51% to encorafenib alone. Objective response rates to BRAF/MEK combo's in other studies have ranged from 48-70%, depending. OS data for encorafenib/binimetinib has not yet been reported. OS in most other BRAF/MEK combo's is around 2 years. The combo discussed here demonstrated fewer side effects than when the BRAFi component was used alone....which is consistent with other reports using a BRAF/MEK combo vs BRAFi alone.
PFS of 14.9 months is better than 12. Wish they had allowed testing in a greater swath of patients. (But I say that about most all trials!!!) We'll have to see what the OS data shows and if these current figures hold in future cohorts. Hang tough ratties. You will save us all. - c
So....yep. Pretty good sum up, I'd say. STILL have no OS data. Which is possibly good...in that they are having to watch it a long time, because these ratties are still trucking! Or, possibly not good...and Array and the researchers just haven't wanted to put it out there yet! (Oh, yeah...I'm definitely in the pocket of Big Pharma, right? Just a little inside MPIP humor there!!!) Hopefully, those numbers will be good and the Encorafenib/Binimetinib BRAF/MEK combo will be an improvement over current BRAF/MEK combo's for BRAF positive melanoma peeps. However, the problem with this trial is just as it so often is with others:
1. We don't compare apples to apples.
2. We leave out folks (brain mets, LMD, ocular, and mucosal melanoma patients) in serious need....cause WHY???? (Yeah, I actually know. Those folks do not respond as well to most current therapies and make your products look bad don't they Array, BMS, Merck...and all the rest of you???)
3. We don't base trial questions on what we already KNOW!!!
4. Results are slow in coming.
5. We saw the same logs over and over.
Now, BACK TO TODAY ~ I don't think this approval is necessarily a bad thing at all!!! But....I do believe in truth in advertising.
Here are a few more deets from the package insert: OOOOOPS! Is Array inept or not providing full disclosure???!!! Cause.....no matter how I look it up, I have not succeeded in finding a working link to the prescribing info for BRAFTOVI, only the one for MEKTOVI seems to be working. So, I'll suffice it to say that these are basically new BRAF/MEK inhibitors that should be given together for folks with BRAF positive (V600E or V600K) melanoma which is about half of us. They are administered orally. They come with about the same side effect profile as all the other BRAF/MEK combo products.
Here's hoping that many melanoma peeps benefit from the combo. Here's hoping that someday, clinical trials will be set up in such a way that folks who MIGHT benefit are NOT excluded, that apples are compared to apples, that pharma will realize that we ratties are NOT stupid and can see very clearly when they stack the deck in their favor.
For what it's worth. - c