› Forums › General Melanoma Community › BRAF after BRAF
- This topic has 21 replies, 4 voices, and was last updated 12 years, 5 months ago by
taron.
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- November 17, 2011 at 8:48 pm
Dear All,
I wanted to ask if anyone is aware of a succesful rechallange to a BRAF inihibitor.
There is one case in Europe in Belgium which is summarised here (see post from Quentin) but basically Quentin went from Braf inihibitors to ipi and back to inihibitors. I am a stage 4 currently on Vemurafenib and obviously very interested in the whole resistance issue.
Dear All,
I wanted to ask if anyone is aware of a succesful rechallange to a BRAF inihibitor.
There is one case in Europe in Belgium which is summarised here (see post from Quentin) but basically Quentin went from Braf inihibitors to ipi and back to inihibitors. I am a stage 4 currently on Vemurafenib and obviously very interested in the whole resistance issue.
Given how new these drugs are there may not be that many people that have had a chance to try all these treatments so I decided to ask patients group if there are any other cases. Sure the docs will write about these cases, but will they do that in time for me and my family?
So I would like to ask you to reply to this thread if you are aware of any such case where someone who had previously progressed on a BRAF or BRAF and MEK combo then managed, somehow to respond again.
Thank you
Taron
- Replies
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- November 21, 2011 at 5:08 am
The docs won't work outside their trial protocols…some trials are combining the drugs, so those might actually do that for you.Like my trial won't allow previous use of Ipi or anti PD 1, but they run a sister trial that does allow ipi in a later arm of the trial. I think the mixing of drug thing isn't that it might harm you, but its for the drug companies to credit their drug as the one that is working. Previous use of another drug might cloud the results….Just my thought only. Lynn
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- November 21, 2011 at 5:08 am
The docs won't work outside their trial protocols…some trials are combining the drugs, so those might actually do that for you.Like my trial won't allow previous use of Ipi or anti PD 1, but they run a sister trial that does allow ipi in a later arm of the trial. I think the mixing of drug thing isn't that it might harm you, but its for the drug companies to credit their drug as the one that is working. Previous use of another drug might cloud the results….Just my thought only. Lynn
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- November 21, 2011 at 5:08 am
The docs won't work outside their trial protocols…some trials are combining the drugs, so those might actually do that for you.Like my trial won't allow previous use of Ipi or anti PD 1, but they run a sister trial that does allow ipi in a later arm of the trial. I think the mixing of drug thing isn't that it might harm you, but its for the drug companies to credit their drug as the one that is working. Previous use of another drug might cloud the results….Just my thought only. Lynn
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- November 21, 2011 at 6:50 pm
been asking the same questions and haven't got any straight answers…all i know is the cascade sequence of protein mutations…that is b-raf to mek and then jump perhaps to c-kit mutation or somewhere else…i think when mine fails, since targeted therapy works for me so far ,is to get retested for mutations at that point…try to pinpoint the place of mutation so i can pinpoint the drug…to take…hopefully by this time the researchers will be a little more ahead of the 'evil'
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- November 21, 2011 at 8:16 pm
Hi boot2aboot and Lynn,
The example in Belgium shows that at least for some, resistance may not genetic (since one would assume that it is highly unlikely your tumor mutates and therefore you develop resistance and then after w while you have a second mutation that brings you back exactly where you started). I believe this is what is called epigenetics.
That said mine and other oncologysts also check for a new mutation upon resistance, which leads me to believe that there must be some evidence that for some, resistance can be explained genetically.
Since we are trailblazing, and nobody knows (including our dr's) what's necessarily the best option, I want to learn as much as possible and moreover I think we as patients can help the dr's community (and ourselves) by sharing patients cases before they are published – to maximise the chances that we will also benefit from that knowledge, not just those that come after. The internet's speed must more useful than just to know what Jay-z is up to on twitter.
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- November 21, 2011 at 8:16 pm
Hi boot2aboot and Lynn,
The example in Belgium shows that at least for some, resistance may not genetic (since one would assume that it is highly unlikely your tumor mutates and therefore you develop resistance and then after w while you have a second mutation that brings you back exactly where you started). I believe this is what is called epigenetics.
That said mine and other oncologysts also check for a new mutation upon resistance, which leads me to believe that there must be some evidence that for some, resistance can be explained genetically.
Since we are trailblazing, and nobody knows (including our dr's) what's necessarily the best option, I want to learn as much as possible and moreover I think we as patients can help the dr's community (and ourselves) by sharing patients cases before they are published – to maximise the chances that we will also benefit from that knowledge, not just those that come after. The internet's speed must more useful than just to know what Jay-z is up to on twitter.
-
- November 21, 2011 at 8:16 pm
Hi boot2aboot and Lynn,
The example in Belgium shows that at least for some, resistance may not genetic (since one would assume that it is highly unlikely your tumor mutates and therefore you develop resistance and then after w while you have a second mutation that brings you back exactly where you started). I believe this is what is called epigenetics.
That said mine and other oncologysts also check for a new mutation upon resistance, which leads me to believe that there must be some evidence that for some, resistance can be explained genetically.
Since we are trailblazing, and nobody knows (including our dr's) what's necessarily the best option, I want to learn as much as possible and moreover I think we as patients can help the dr's community (and ourselves) by sharing patients cases before they are published – to maximise the chances that we will also benefit from that knowledge, not just those that come after. The internet's speed must more useful than just to know what Jay-z is up to on twitter.
-
- November 21, 2011 at 8:16 pm
Hi boot2aboot and Lynn,
The example in Belgium shows that at least for some, resistance may not genetic (since one would assume that it is highly unlikely your tumor mutates and therefore you develop resistance and then after w while you have a second mutation that brings you back exactly where you started). I believe this is what is called epigenetics.
That said mine and other oncologysts also check for a new mutation upon resistance, which leads me to believe that there must be some evidence that for some, resistance can be explained genetically.
Since we are trailblazing, and nobody knows (including our dr's) what's necessarily the best option, I want to learn as much as possible and moreover I think we as patients can help the dr's community (and ourselves) by sharing patients cases before they are published – to maximise the chances that we will also benefit from that knowledge, not just those that come after. The internet's speed must more useful than just to know what Jay-z is up to on twitter.
-
- November 21, 2011 at 8:16 pm
Hi boot2aboot and Lynn,
The example in Belgium shows that at least for some, resistance may not genetic (since one would assume that it is highly unlikely your tumor mutates and therefore you develop resistance and then after w while you have a second mutation that brings you back exactly where you started). I believe this is what is called epigenetics.
That said mine and other oncologysts also check for a new mutation upon resistance, which leads me to believe that there must be some evidence that for some, resistance can be explained genetically.
Since we are trailblazing, and nobody knows (including our dr's) what's necessarily the best option, I want to learn as much as possible and moreover I think we as patients can help the dr's community (and ourselves) by sharing patients cases before they are published – to maximise the chances that we will also benefit from that knowledge, not just those that come after. The internet's speed must more useful than just to know what Jay-z is up to on twitter.
-
- November 21, 2011 at 8:16 pm
Hi boot2aboot and Lynn,
The example in Belgium shows that at least for some, resistance may not genetic (since one would assume that it is highly unlikely your tumor mutates and therefore you develop resistance and then after w while you have a second mutation that brings you back exactly where you started). I believe this is what is called epigenetics.
That said mine and other oncologysts also check for a new mutation upon resistance, which leads me to believe that there must be some evidence that for some, resistance can be explained genetically.
Since we are trailblazing, and nobody knows (including our dr's) what's necessarily the best option, I want to learn as much as possible and moreover I think we as patients can help the dr's community (and ourselves) by sharing patients cases before they are published – to maximise the chances that we will also benefit from that knowledge, not just those that come after. The internet's speed must more useful than just to know what Jay-z is up to on twitter.
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- November 22, 2011 at 8:01 pm
all i know is melanoma is smart (why it is the worst of the worst cancers )and finds it's way around drugs…the only way i can see how this happens is through mutations…but, i am not a scientist,,,, it just makes sense to me…and i know researchers keep looking at targeted therapies as opposed to blanket therapies, combinations of blanket and target therapies because they suspect this (mutations) to be happening but, don't yet know the actual reasons why…they suspect that melanomas 'jump' protein sequences…if and when i fail zelboraf, then i would (after consultation ) lean towards the braf-mek trial asap…
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- November 27, 2011 at 5:26 pm
The problem is that there won't be many cases where this has been tried (just because of the study protocols, liability etc.)
For those in the EU, if you responded previously to a BRAF inhibitor (from Roche/GSK/…) and stopped responding a while ago, it may be worth asking your oncologist to get in touch with Roche to see if you can be enrolled in the Vemurafenib expanded access programme (BRIM4).
It is only when patients try it that other cases can be found. From a patient point of view, if you have no other treatment lined up, you have nothing to lose. One knows pretty quicky if there is a response again or not (if you have skin lesions).
Please reply to the thread if you managed to get on BRIM4 and respond again.
Thank you,
Peter (Stage 4, lung, skin and brain mets and just became Vemurafenib resistant)
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- November 27, 2011 at 5:26 pm
The problem is that there won't be many cases where this has been tried (just because of the study protocols, liability etc.)
For those in the EU, if you responded previously to a BRAF inhibitor (from Roche/GSK/…) and stopped responding a while ago, it may be worth asking your oncologist to get in touch with Roche to see if you can be enrolled in the Vemurafenib expanded access programme (BRIM4).
It is only when patients try it that other cases can be found. From a patient point of view, if you have no other treatment lined up, you have nothing to lose. One knows pretty quicky if there is a response again or not (if you have skin lesions).
Please reply to the thread if you managed to get on BRIM4 and respond again.
Thank you,
Peter (Stage 4, lung, skin and brain mets and just became Vemurafenib resistant)
-
- November 27, 2011 at 5:26 pm
The problem is that there won't be many cases where this has been tried (just because of the study protocols, liability etc.)
For those in the EU, if you responded previously to a BRAF inhibitor (from Roche/GSK/…) and stopped responding a while ago, it may be worth asking your oncologist to get in touch with Roche to see if you can be enrolled in the Vemurafenib expanded access programme (BRIM4).
It is only when patients try it that other cases can be found. From a patient point of view, if you have no other treatment lined up, you have nothing to lose. One knows pretty quicky if there is a response again or not (if you have skin lesions).
Please reply to the thread if you managed to get on BRIM4 and respond again.
Thank you,
Peter (Stage 4, lung, skin and brain mets and just became Vemurafenib resistant)
-
- November 22, 2011 at 8:01 pm
all i know is melanoma is smart (why it is the worst of the worst cancers )and finds it's way around drugs…the only way i can see how this happens is through mutations…but, i am not a scientist,,,, it just makes sense to me…and i know researchers keep looking at targeted therapies as opposed to blanket therapies, combinations of blanket and target therapies because they suspect this (mutations) to be happening but, don't yet know the actual reasons why…they suspect that melanomas 'jump' protein sequences…if and when i fail zelboraf, then i would (after consultation ) lean towards the braf-mek trial asap…
-
- November 22, 2011 at 8:01 pm
all i know is melanoma is smart (why it is the worst of the worst cancers )and finds it's way around drugs…the only way i can see how this happens is through mutations…but, i am not a scientist,,,, it just makes sense to me…and i know researchers keep looking at targeted therapies as opposed to blanket therapies, combinations of blanket and target therapies because they suspect this (mutations) to be happening but, don't yet know the actual reasons why…they suspect that melanomas 'jump' protein sequences…if and when i fail zelboraf, then i would (after consultation ) lean towards the braf-mek trial asap…
-
- November 21, 2011 at 6:50 pm
been asking the same questions and haven't got any straight answers…all i know is the cascade sequence of protein mutations…that is b-raf to mek and then jump perhaps to c-kit mutation or somewhere else…i think when mine fails, since targeted therapy works for me so far ,is to get retested for mutations at that point…try to pinpoint the place of mutation so i can pinpoint the drug…to take…hopefully by this time the researchers will be a little more ahead of the 'evil'
-
- November 21, 2011 at 6:50 pm
been asking the same questions and haven't got any straight answers…all i know is the cascade sequence of protein mutations…that is b-raf to mek and then jump perhaps to c-kit mutation or somewhere else…i think when mine fails, since targeted therapy works for me so far ,is to get retested for mutations at that point…try to pinpoint the place of mutation so i can pinpoint the drug…to take…hopefully by this time the researchers will be a little more ahead of the 'evil'
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- November 29, 2011 at 12:04 pm
This recent paper from Flaherty, Ribas and co. may explain why some people may get a second response to BRAF inhibitors http://
http://www.ncbi.nlm.nih.gov/ pubmed/22113612 Also we understood from Roche that at least in EU they may be open to accept patients – under certain conditions to be confirmed – to "reinduced" inside their EAP.
Please discuss with your doctors as an option for patients who have already progressed on a BRAF iihibitor (either Roche or GSK). For some – like for Quentin – this could be a lifeline when all other treatment options have been exhausted. For the patients and research community this will accelerate the understanding of the mechanisms of resistence and hopefully the identification of ways around them.
Stay strong.
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- November 29, 2011 at 12:04 pm
This recent paper from Flaherty, Ribas and co. may explain why some people may get a second response to BRAF inhibitors http://
http://www.ncbi.nlm.nih.gov/ pubmed/22113612 Also we understood from Roche that at least in EU they may be open to accept patients – under certain conditions to be confirmed – to "reinduced" inside their EAP.
Please discuss with your doctors as an option for patients who have already progressed on a BRAF iihibitor (either Roche or GSK). For some – like for Quentin – this could be a lifeline when all other treatment options have been exhausted. For the patients and research community this will accelerate the understanding of the mechanisms of resistence and hopefully the identification of ways around them.
Stay strong.
-
- November 29, 2011 at 12:04 pm
This recent paper from Flaherty, Ribas and co. may explain why some people may get a second response to BRAF inhibitors http://
http://www.ncbi.nlm.nih.gov/ pubmed/22113612 Also we understood from Roche that at least in EU they may be open to accept patients – under certain conditions to be confirmed – to "reinduced" inside their EAP.
Please discuss with your doctors as an option for patients who have already progressed on a BRAF iihibitor (either Roche or GSK). For some – like for Quentin – this could be a lifeline when all other treatment options have been exhausted. For the patients and research community this will accelerate the understanding of the mechanisms of resistence and hopefully the identification of ways around them.
Stay strong.
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