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February 1, 2013 at 2:25 pm #20983KarenJParticipant
My husband has stage IV, with mets to his lungs, liver, and brain. He had whole brain radiation and steroid. He is off the steroid and finished with the radiation treatments. He has the BRAF mutation, so is considering the clinical trial evaluating the combination of Zel and Ipi. Will beginning that trial preclude use of Dabrafenib when it’s approved? The evidence of Dabrafenib crossing the blood/brain barrier makes it seem the better choice. Or should I pursue a trial of Dabrafenib? We live in the southwest, and so many of the trials are so far away. Or is PD-1 a better choice?February 1, 2013 at 5:32 pm #58913 Zelboraf and dabrafenib are very similar drugs and they target the same BRAF mutation; they’re just made by different companies. They both cross the blood-brain barrier. I think your husband will do just as well on Zelboraf as on dabrafenib.
Zelboraf and dabrafenib only work in about 60% of the patients who take it but when it works, it works quickly and well. It does kill brain mets. However, melanoma tends to become resistant to the drug in 6-8 months. Ipi, on the other hand, is an antibody that stimulates the immune system. It takes longer to have an effect, but the effect lasts longer than Zelboraf, sometimes for a couple of years. So a combination of Zel and ipi might be a good thing to try. The problem, of course, would be side effects. Some early reports say that the combo trial results in liver damage or skin damage in some patients. If your husband decides to try this combo, but certain that you know the danger signs of side effects to watch out for and that you have access to a local medical center experienced in handling the side effects of both Zel and ipi.February 1, 2013 at 11:15 pm #58914AnonymousGuest
Hi Karen. While reading you posting, I’m still struck by the fact the we have so many choices today that were just not available just a few years ago. Also, the PD-1, and combo trials are really starting to proliferate. That’s real hope.
Pat’s advice is solid gold.
Where do you live in the SW? The Angeles Clinic is well respected, with many trials and may be within reach of you guys:
JeffFebruary 2, 2013 at 1:24 am #58915KarenJParticipant
I had thought that Zelboraf and dabrafenib must be similar, but had no information on Zelboraf crossing the blood/brain barrier. Thank you, Pat, for that information. It is very heartening.
I am very concerned about the side effects, and will need to find out what the symptoms are. It’s really good advice to verify the ability of the cancer center here to handle those side effects.
Thanks, Jeff, for that link. I will look into it this evening. We live in New Mexico, and my husband is being treated at UNM Cancer Center. There is a group of melanoma specialists there. Another local option is a branch of MD Anderson. I have not pursued that option yet, because the melanoma researchers at UNM were recommended to me and we went there first.
Thank you both for your being so generous with your time and experience, to share this information with me.February 2, 2013 at 3:11 pm #58916
Welcome to our forum. I don’t like to disagree with Pat, but truly, none of the options out there have been proven to significantly cross the blood-brain barrier. Dabrafenib by GSK did show in a small study (15) to have some activity with brain mets. I haven’t seen any studies on Zelboraf (Genentech) doing so. They are two different braf agents and combined with MEK or other agents may provide further response. Our bodies are built with these barriers for a reason (the placenta is another one) and they are tough to penetrate. (another therapy is Temodar that is used for brain cancer, a type of dacarbazine but not well proven in trials to have brain met activity.) For now, we really can only rely on radiation as working well for brain mets.
You are at a tough crossroads in choosing a therapy. The dabrafenib/mek drugs by GSK may be approved by the FDA shortly, next few months we hope. So you could stay at home and get them by perscription down the road. Zelboraf and IPI (Yervoy) have already been approved by the FDA, so they can be prescribed now. Perhaps with his condition being serious, you want to stick nearby and try the Zel/IPI combo to start. (although not a proven combo) PD1 has about a 30% (possibly higher but not known) response rate. IPI/Yervoy has about a 15% response rate. And Zelboraf has a 48% response rate.
As for top centers on the West coast, I would recommend Dr. Ribas at UCLA for compassion and expertise:
The Angeles clinic does have a large amount of trials too and their split off, Dr. O’Day has a center, Beverly Hills Cancer Center in Hollywood as well. All three have the Merck PD1. http://www.cancer.ucla.edu/index.aspx?page=645&recordid=214
I hope this information helps you understand these many options which as Jeff points out weren’t available until recently. I pray we have more to offer in the near future! We are here to help you, let us know how things are going for you.February 2, 2013 at 5:51 pm #58917
Regarding dabrafenib’s activity against brain mets, I was referring to the abstract presented at last summer’s ASCO meeting: “Dabrafenib Extends Progression-Free Survival in Metastatic Melanoma, Has High Clinical Activity in Brain Metastases” http://chicago2012.asco.org/ASCODailyNews/LBA8500.aspx
Admittedly, this is only the BREAK-MB Phase II study of 172 patients and not a peer-reviewed Phase III study, but the data looks pretty good to me.
Seeing how well GSK’s dabrafenib was working on brain mets, Genetech immediately launched a clinical trial to see if Zelboraf (vemurafenib) also worked on brain mets because they had excluded all patients with brain mets from their original clinical trials. I have not seen any published reports yet, but our oncologist at Moffitt said it was going well and, in point of fact, Zelboraf did shrink my brother’s brain tumors. Mere anecdote, of course, but true.
I agree with Catherine that the jury is still out about these treatments for brain tumors. However, my advice was not made up of whole cloth, either. When patients and their families have to make tough choices and/or beat the bushes to find appropriate, promising clinical trials, even preliminary data can be helpful.February 2, 2013 at 6:32 pm #58918Quote:PatW wrote:
Zelboraf and dabrafenib are very similar drugs and they target the same BRAF mutation; they’re just made by different companies. They both cross the blood-brain barrier. I think your husband will do just as well on Zelboraf as on dabrafenib.
Zelboraf and dabrafenib only work in about 60% of the patients who take it but when it works, it works quickly and well. It does kill brain mets
Pat/ et al,
This is what I am responding to. Zelboraf and Dabrafenib are not very similar, although both BRAF agents. We truly don’t know that both cross the blood-brain barrier nor that they conclusively kill brain mets. The study you mention looks very good for dabrafenib, but I’ve heard it downplayed to a few patients. Just to set the record straight, neither have 60% response rates. Zelboraf has been shown to have a 48% response rate. I wish we had an agent with 60% response rate! Unless you’ve seen a study I haven’t. So we try to be careful here and not raise false hope about therapies. There is so much we still don’t know about these new agents.February 2, 2013 at 8:16 pm #58919
I certainly didn’t mean to raise any false hopes. The OP (Karen) was trying to decide whether her husband should go for a Zel + ipi trial or hold out for a Dabrafenib trial. I was just giving her food for thought. However, I defer to Catherine’s superior depth and breadth of knowledge in these matters.February 2, 2013 at 9:22 pm #58920bettinParticipant Dear all,
I would think that the combination of a form of immunotherapy (like Ipi) and a targeted agent (like a BRAF inhibitor) makes absolute sense because they ideally complement their advantages while compensating for their disadvantages. Immunotherapy often only works with a delay but has the potential for long-term efficacy while targeted therapy works quickly but comes with resistance after a while.
So ‘buying’ time with a targeted agent to give the immunotherapy time to kick in makes perfect sense and is in my mind preferable to monotherapy.
Once a drug is approved, previous treatment with a similar agent should also not exclude you from having access to it- that’s trial stipulations- unless of course you had serious side effects under the first one.
BRAF inhibitors do work in brain mets- the studies have been quoted- there has been a discussion whether it is due to the substance passing the blood/brain barrier or the immune system kicking in. To be honest, I wouldn’t wait to find out whether it works in my own case but get the mets treated ideally with Gamma Knife (there’s an excellent webinar on this on this website) and take the targeted agent on top.
As for the discussion about side effects, let’s not forget that also NOT treating Melanoma comes with ‘side effects’.
Wishing you all the best-
BettinaFebruary 3, 2013 at 12:40 am #58921Celeste MorrisParticipant
Perfectly put, Bettina. Best of luck to you and your husband, Karen. This board will continue to give you good information as you proceed. Hang in there. cFebruary 3, 2013 at 5:40 am #58922NYKarenParticipant Hi Karen,
I’m sorry that I’m just seeing this now.
I agree with Bettina’s advice about Gamma Knife first, at least then you wouldn’t have to worry if one treatment is more effective than another in crossing the blood-brain barrier.
I know of several people who have started with Zelboraf, because when it works, it works very quickly, and for various reasons gone on to ipi. As for side-effects, from what I’ve read and from personal experience, they vary greatly by individual.
Please keep us posted,
Karen (the one in NY:))February 3, 2013 at 1:25 pm #58923
Karen’s husband already had whole brain radiation, so gamma knife wouldn’t be a solution right now for them. I hope that they find a good solution to get him started.
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