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March 7, 2013 at 8:53 pm #21087
I was wondering if anyone has any updates on FDA approval for the GSK combo? Catherine?? The last I heard was late first quarter 2013, but time’s a-ticking…
There are still some raised lesions on my face (Dr. Halpern took a couple yesterday for biopsy) and I’m getting anxious about Zelbarof, although he did comment that nobody he knows has ever progressed after only one month on Zel! I then spent about 1/2 hour with one of his nurses trying to compare last visit’s photos to yesterday,s, but since they were taken with different cameras and in different light, it was impossible to tell…but we pretty much decided that nothing’s changed. I look at it every day and say to myself “Is that one more raised, flatter…who knows? I do know that I’m driving myself crazy!
I know that the combo is my Plan B for now, so hopefully someone has news. We were trying 3 weeks on, 2 weeks off Zel because it worked in a mouse trial for extending response to Zel. However, today on my visit to Dr. Wolchok, we discussed my growing anxiety, and that since this has only shown to be the case in mice, I’m not really interested in being among the first human test-cases, so I’ve resumed 3/3 with no breaks.
best wishes to all,
KarenMarch 7, 2013 at 10:42 pm #59507Catherine PooleKeymaster
Sorry, no news yet. I’ll let you know when I hear it!March 8, 2013 at 12:05 am #59508 Thanks, Catherine.
Was it like this– all the waiting, wondering and speculating– before Yervoy and Zelboraf were approved?
KarenMarch 8, 2013 at 1:22 am #59509Catherine PooleKeymaster
Yes, the FDA and pharma are very quiet about these things until they happen. But approvals have been very quick to happen so stay tuned! I’m hoping it will happen asap too!April 3, 2013 at 5:16 am #59510 I saw that the FDA’s ‘scheduled date’ (which I assume means thereabouts) for decision is June 3 for GSK’s Dabrafenib (BRAF inhibitor). I remember it because if not approved until then it would just miss ASCO.
The same date, June 3, also appears for the FDA’s expected decision on GSK’s Trametinib (MEK inhibitor). They are two separate submissions.
These drugs are in for monotherapy approval not combotherapy, as the c. trials gathering data for submission for combotherapy approval are not yet far enough along to have enough data for that submission. So the decisions that will be rendered yeah or nay are for separate drug approvals, for monotherapy, but hopefully both drugs will get approval which would then at least make it possible for oncos to go off-label and prescribe both at the same time since preliminary results in the ongoing combotherapy c. trials are showing that BRAF-MEK combo therapy is more effective than either drug as a monotherapy. (Unless of course you are BRAF negative which then only the MEK drug could be useful.)
I am presently in the Phase 2 clinical trial for GSK’s Dabrafenib/Trametinib combotherapy. I’m on the highest dose (150mg 2x day and 2mg 1x day) and just celebrated my 2 year anniversary on this regimen this month! Yeah !!! Prior to combo therapy I was on BRAF monotherapy which lasted the typical 7 months before progression of disease – so combining both of these c. trials it has been 2 years and 7 months that these GSK drugs have been holding off the melanoma. So to those of you waiting for these drugs – hang in there as there is hope. And since the side effect profile has been so mild on these therapies and the results so much better than anything else in this class approval would seem likely for both of them I would think.April 3, 2013 at 11:08 am #59511
What great news to wake up to!
Thank you so much for posting this, and congratulations on your 2 years in the trial!
I know a lot of people will be happy to read this.
KarenApril 5, 2013 at 11:53 am #59512ncdanielParticipant
Does the GSK approval effect BRAF negative people. I read about MEK part but not sure what all this means can anyone tell me if this will be effective for Braf negative?April 5, 2013 at 2:23 pm #59513GillyParticipant Can i just ask (my hubby is also on the Combi V trial but is on the Zelboraf arm) whether they have a response rate for the Dab/Tram combination – I know its early days but there must be some ideas out there – I thought the zelboraf had a relatively high response rate but then tended to time out at 7-9 months – is the response rate for the Braf/MEK combination the same – I know the response time seems to be more long lasting . Thanks.April 5, 2013 at 3:43 pm #59514ncdaniel wrote:
Does the GSK approval effect BRAF negative people. I read about MEK part but not sure what all this means can anyone tell me if this will be effective for Braf negative?
The BRAF inhibitor drugs are for ‘BRAF +’ patients which means the mutation is V600E and not wildtype. Some early GSK studies have also given a few V600K folks the BRAF drug to see what happened, it did not have the same success as the V600E people and I am not even sure if they are planning to do that again in the future. For the approx 40-50% of cutaneous melanomas that are V600E the response rate has been approx 30-40% (depending on whether Roche’s Vemurafenib or GSK’s Dabrafenib, and I believe that GSK’s drug has had more efficacy and less side effects than Roche’s. Unfortunately this drug is really meant at this time for the BRAF+ people.
But since the MEK drug has shown not to need the BRAF+ status to work on some people that probably can be given to BRAF- people. Will have to wait and see what the FDA says about that when they render their decision in a few weeks.April 5, 2013 at 4:25 pm #59515Gilly wrote:
Can i just ask (my hubby is also on the Combi V trial but is on the Zelboraf arm) whether they have a response rate for the Dab/Tram combination – I know its early days but there must be some ideas out there – I thought the zelboraf had a relatively high response rate but then tended to time out at 7-9 months – is the response rate for the Braf/MEK combination the same – I know the response time seems to be more long lasting . Thanks.
It seems that both BRAF inhibitor drugs, Vermurafenib (Roche) and Dabrafenib (GSK), have a median response rate about 7 months. Too bad of course that they don’t last forever (wouldn’t that be nice!) , but 7 months is a big improvement over other things before these drugs came along. You have to look at it that it gives us patients another 7 months of time for the scientific community to continue their advances in treatment and for more studies to open that we can go into ‘for another extension’ of time, etc etc.
The BRAF/MEK combo has a longer median response rate than either drug given as a mono therapy (BRAF or MEK alone). But – there are a fair amount of us who are much further out than the 11 month (or thereabouts) median, like 1 1/2 years – 3 years
So if you cannot get into a BRAF/MEK combo study once the drugs are FDA approved as monotherapies ask your doc to prescribe them as a combo off label therapy. It is purported at this point in time that since the stats for the combo are so much higher than either drug as a monotherapy that in the future the combo will become the standard of care for BRAF+ folks. The highest dose level in the combo study of Dabrafenib (BRAF) 150mg 2x day and Trametinib 2mg 1x day (am) has shown to be more effective than lower dose levels and the side effects are still easily tolerable even at this higher dose.
Since the BRAF/MEK combo studies are much younger than the initial single drug studies only 1 comprehensive summary paper from the ongoing Phase 2 study has been published so far. It is an excellent article, very comprehensive and very detailed, so do try to get a copy of it to read even if you have to pay for it.
New England Journal of Medicine: Sept 29 2012
Lead Authors: Flaherty and Infante
Title: COMBINED BRAF AND MEK INHIBITION IN MELANOMA WITH BRAF V600 MUTATIONSApril 5, 2013 at 4:52 pm #59516
Here’s the link to the BRAF/MEK combo report NEJM article: (the full article is not here, you have to have a NEJM subscription or purchase the article to get all 10 pages of summary charts and graphs, conclusions, etc) if this topic interests you. It also spends some time quoting summary numbers from other c. trials on BRAF mono and MEK mono stats (for those of you BRAF- folks perhaps considering MEK mono therapy.) A very comprehensive article overall.April 5, 2013 at 9:01 pm #59517 Dear JR4seasons,
Thanks for the great information. I am not so familiar with off-label prescribing; you mention that the GSK BRAF inhibitor has fewer side effects than Zelbarof; that alone is a reason to switch! But as for adding the MEK drug, does being prescribed an off-label drug have more of a chance of an insurance company denying it? So far my ins co has been fine about paying $10,000/month for Zel, but I’m concerned about the future.
Any insights greatly appreciated.
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