› Forums › General Melanoma Community › After Zelboraf
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NYKaren.
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- December 31, 2011 at 8:57 pm
Hi to All taking Zelboraf and those who research MM, especially Michael, Charlie, Gene, Dick K and Jimmy B.,
Hi to All taking Zelboraf and those who research MM, especially Michael, Charlie, Gene, Dick K and Jimmy B.,
I am currently ending my 4th month of Zelboraf treatment. I saw the onc and had my second set of scans. The GOOD news is that my tumors have shrunk 40% and my bloodwork looks good…I have one tumor in my liver measuring .6X.9cm (was.8X1.3 in OCT). I have one tumor in my spleen which was 1X1cm(was1X1.5 OCT) i have 4 lung mets? nodules the largest being 3m (no change from OCT)… So i would say i had a 40% reduction in my liver and spleen mets…not bad considering i am on a GREATLY reduced dose of Zel due to severe side effects….i was advised to start searching clinical trials because Zelboraf usually quits working after 6 mos…I will head down to Moffitt and consult with Bowtie Guy…
Here are my questions
1. is surgery for liver and spleen met a smart way to go? ( the only reason i ask is i have one tumor in each organ and they are small)…but i have no idea what the recovery time will be…and that would be important because i could have no treatment during this time…the lung mets are too small to biopsy and they might not even be mel…but, of course, i will claim they are…because they might be…for stage 4 trials…
2. If i do surgery can i still get into anti-PD1 trial? or will that boot me out?
3. If i do surgery should i consider IL-2 instead of PD1?-the only reason i ask this is because IL-2, although it works in 5% of peeps seems to create NED in those it does work…
4, is any science guy out there currently on to finding a way to target other pathways like CTL4, ect? Just HOW many pathways is there anyway? other than Braf Mek pathway, PD-1, CTL4?????
4.instead of anti-PD1 should i consider MEK trial (since i am Braf +)
Happy Melanoma Free and New EFFECTIVE TREATMENT 2012 everyone…We lost a lot of Great People this year and i don't want to lose anyone else , including me to MM.
Boots
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- December 31, 2011 at 9:28 pm
Boots,
I don't have any suggestions but I just wanted to let you know that I hope you continue to have success with shrinkage.
In the past I have had surgery, my scans are this coming Tuesday. My oncologist has agreed in my past as long as I haven't shown progression when it's only one time and gives me 6 months before I have shown it again. I'm not sure how your Dr might be thinking of 3 different organs. You might still might want to bring it up.
Dealing with my brain met I am now weaning the steroids on Friday to .5. My fear is that I need to start something systemic and I know that it needs to be totally weaned first.
Have a happy New Years!
Linda
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- December 31, 2011 at 10:29 pm
Boots, Since you are responding to the BRAF therapy, you may want to see if you qualify for a MEK and or ERK or a combination of.
The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence
Abstract
Historically, patients with advanced cutaneous melanoma have a poor prognosis and limited treatment options. The discovery of selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation as an oncogenic mutation in cutaneous melanoma and the importance of the mitogen-activated protein kinase (MAPK) pathway in its tumourigenesis have changed the treatment paradigm for melanoma. Selective BRAF inhibitors and now MEK inhibitors have demonstrated response rates far higher than standard chemotherapeutic options and we review the phase I–III results for these agents in this article. The understanding of mechanisms of resistance that may occur upstream, downstream, at the BRAF level or bypassing the MAPK pathway provides a platform for rational drug development and combination therapies.
You may want contact the Paper's author, Dr. Lemech for a copy of the paper
Therapeutic Advances in Medical Oncology
best regards
Jimmy B
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- January 3, 2012 at 1:03 am
Jim, Happy New Year and i hope it's not our last!!!!
i can get into a MEK only trial at my oncs now…but, ERK-MEK combo sounds interesting…the problem is…when MM mutates which way does it normally go in Brafy people??? does it stay on Raf pathway or jump to CTl4? or goodness knows whatever else pathways…that is the million dollar question so i am back to crap shooting again…and one of the reasons i wanted the existing stuff cut out first…still trying to sort out pathways and how it jumps…need to bone up on all those webinars. Thank you for your suggestion…i have already spoken to the clinical trial nurse in nashville and i was very impressed that they do a full set of genetic tests on MM…i have ONLY had braf done in Ohio.
boots….
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- January 3, 2012 at 1:03 am
Jim, Happy New Year and i hope it's not our last!!!!
i can get into a MEK only trial at my oncs now…but, ERK-MEK combo sounds interesting…the problem is…when MM mutates which way does it normally go in Brafy people??? does it stay on Raf pathway or jump to CTl4? or goodness knows whatever else pathways…that is the million dollar question so i am back to crap shooting again…and one of the reasons i wanted the existing stuff cut out first…still trying to sort out pathways and how it jumps…need to bone up on all those webinars. Thank you for your suggestion…i have already spoken to the clinical trial nurse in nashville and i was very impressed that they do a full set of genetic tests on MM…i have ONLY had braf done in Ohio.
boots….
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- January 3, 2012 at 1:03 am
Jim, Happy New Year and i hope it's not our last!!!!
i can get into a MEK only trial at my oncs now…but, ERK-MEK combo sounds interesting…the problem is…when MM mutates which way does it normally go in Brafy people??? does it stay on Raf pathway or jump to CTl4? or goodness knows whatever else pathways…that is the million dollar question so i am back to crap shooting again…and one of the reasons i wanted the existing stuff cut out first…still trying to sort out pathways and how it jumps…need to bone up on all those webinars. Thank you for your suggestion…i have already spoken to the clinical trial nurse in nashville and i was very impressed that they do a full set of genetic tests on MM…i have ONLY had braf done in Ohio.
boots….
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- December 31, 2011 at 10:29 pm
Boots, Since you are responding to the BRAF therapy, you may want to see if you qualify for a MEK and or ERK or a combination of.
The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence
Abstract
Historically, patients with advanced cutaneous melanoma have a poor prognosis and limited treatment options. The discovery of selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation as an oncogenic mutation in cutaneous melanoma and the importance of the mitogen-activated protein kinase (MAPK) pathway in its tumourigenesis have changed the treatment paradigm for melanoma. Selective BRAF inhibitors and now MEK inhibitors have demonstrated response rates far higher than standard chemotherapeutic options and we review the phase I–III results for these agents in this article. The understanding of mechanisms of resistance that may occur upstream, downstream, at the BRAF level or bypassing the MAPK pathway provides a platform for rational drug development and combination therapies.
You may want contact the Paper's author, Dr. Lemech for a copy of the paper
Therapeutic Advances in Medical Oncology
best regards
Jimmy B
-
- December 31, 2011 at 10:29 pm
Boots, Since you are responding to the BRAF therapy, you may want to see if you qualify for a MEK and or ERK or a combination of.
The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence
Abstract
Historically, patients with advanced cutaneous melanoma have a poor prognosis and limited treatment options. The discovery of selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation as an oncogenic mutation in cutaneous melanoma and the importance of the mitogen-activated protein kinase (MAPK) pathway in its tumourigenesis have changed the treatment paradigm for melanoma. Selective BRAF inhibitors and now MEK inhibitors have demonstrated response rates far higher than standard chemotherapeutic options and we review the phase I–III results for these agents in this article. The understanding of mechanisms of resistance that may occur upstream, downstream, at the BRAF level or bypassing the MAPK pathway provides a platform for rational drug development and combination therapies.
You may want contact the Paper's author, Dr. Lemech for a copy of the paper
Therapeutic Advances in Medical Oncology
best regards
Jimmy B
-
- December 31, 2011 at 9:28 pm
Boots,
I don't have any suggestions but I just wanted to let you know that I hope you continue to have success with shrinkage.
In the past I have had surgery, my scans are this coming Tuesday. My oncologist has agreed in my past as long as I haven't shown progression when it's only one time and gives me 6 months before I have shown it again. I'm not sure how your Dr might be thinking of 3 different organs. You might still might want to bring it up.
Dealing with my brain met I am now weaning the steroids on Friday to .5. My fear is that I need to start something systemic and I know that it needs to be totally weaned first.
Have a happy New Years!
Linda
-
- December 31, 2011 at 9:28 pm
Boots,
I don't have any suggestions but I just wanted to let you know that I hope you continue to have success with shrinkage.
In the past I have had surgery, my scans are this coming Tuesday. My oncologist has agreed in my past as long as I haven't shown progression when it's only one time and gives me 6 months before I have shown it again. I'm not sure how your Dr might be thinking of 3 different organs. You might still might want to bring it up.
Dealing with my brain met I am now weaning the steroids on Friday to .5. My fear is that I need to start something systemic and I know that it needs to be totally weaned first.
Have a happy New Years!
Linda
-
- January 2, 2012 at 8:04 pm
Hey there Boots.
About surgery and IL2, I'm including a video link of a talk my surgical onc gave about surgery and the role of IL-2 in the era of Yervoy and Zelboraf at a recent Aim at Melanoma Conference http://www.youtube.com/watch?v=gOUtIy6T4oM&feature=relmfu.. The audio is a bit weak, so crank up the speakers. So,basically yes, surgery is an option and IL2 is an option, although many trials require measurable disease, few if any rule you out for either surgery or prior IL2 use.
And here is a link to a pretty up-to-date listing of the anti-PD1 trials and the exclusions. http://www.m-icab.org/images/stories/M-ICAB_table_-_final_small.pdf, skip the first listed worthless link. In essence, two weeks out from surgery prior to receiving trial drug.
Of note, many of these PD1 trials exclude prior use of Yervoy, many want an HLA typing of HLA-A02/HLA-A-0201 and many want either/or/and Melan-A, HMB-45, NY-ESO-1 positive tumors, but there is trial that looks at Zelboraf following IPI, go figure. So if you are even considering a future trial, it would be worthwhile now to see how you stack up for those qualifiers.
There are a slew of signaling pathways and a slew of them are being studied; but there is mounting evidence that Braf+ can yield some sensitivity to MEK pathways as well. The problem with pathways is they all have built in redudancies; that is to say though one pathway signal can be blocked, as is the case with V600, each pathway has built in mechanisms to re- route to another pathway, which is why Zelboraf has short term success. Here is another video link from the same conference that discusses signaling pathways http://www.youtube.com/watch?v=BhUXRmLdlvM&feature=relmfu
It is also worthwhile to look at Jerry from Fauq recent post anti-CTLA-4 and Anti-PD-1 antibody
Because I am a fan of IL2,, I found it interesting that in a recent study about PD1 cells http://onlinelibrary.wiley.com/doi/10.1002/eji.201040959/abstract,, it was found that they actually produce IL2. If that is true, it might follow that IL2 could help if you later did get into a PDI trial. Only an opinion.
Lastly, here is a link for an interesting trial for liver mets at MDA that you might find interesting http://www.clinicaltrials.gov/ct2/show/NCT00833807?cond=%22Melanoma%22&rank=185
Probably waaaaaaaaaaaaay more information than you wanted and as always take what you want and leave the rest !
Cheers,
Charlie S
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- January 3, 2012 at 12:48 am
Information is always good, Charlie, and thank you for your input…i know you and King had good success with surgery ….i am leaning on moving down raf pathway suggested by you and Jim …just am stuck between that and PD 1 trials because the initial success rates and i need to study the info on Mek trials better…i know braf jumps to mek jumps to who knows where…thank you…i will post my decision when i make one…
boots
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- January 3, 2012 at 12:48 am
Information is always good, Charlie, and thank you for your input…i know you and King had good success with surgery ….i am leaning on moving down raf pathway suggested by you and Jim …just am stuck between that and PD 1 trials because the initial success rates and i need to study the info on Mek trials better…i know braf jumps to mek jumps to who knows where…thank you…i will post my decision when i make one…
boots
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- January 3, 2012 at 12:48 am
Information is always good, Charlie, and thank you for your input…i know you and King had good success with surgery ….i am leaning on moving down raf pathway suggested by you and Jim …just am stuck between that and PD 1 trials because the initial success rates and i need to study the info on Mek trials better…i know braf jumps to mek jumps to who knows where…thank you…i will post my decision when i make one…
boots
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- January 2, 2012 at 8:04 pm
Hey there Boots.
About surgery and IL2, I'm including a video link of a talk my surgical onc gave about surgery and the role of IL-2 in the era of Yervoy and Zelboraf at a recent Aim at Melanoma Conference http://www.youtube.com/watch?v=gOUtIy6T4oM&feature=relmfu.. The audio is a bit weak, so crank up the speakers. So,basically yes, surgery is an option and IL2 is an option, although many trials require measurable disease, few if any rule you out for either surgery or prior IL2 use.
And here is a link to a pretty up-to-date listing of the anti-PD1 trials and the exclusions. http://www.m-icab.org/images/stories/M-ICAB_table_-_final_small.pdf, skip the first listed worthless link. In essence, two weeks out from surgery prior to receiving trial drug.
Of note, many of these PD1 trials exclude prior use of Yervoy, many want an HLA typing of HLA-A02/HLA-A-0201 and many want either/or/and Melan-A, HMB-45, NY-ESO-1 positive tumors, but there is trial that looks at Zelboraf following IPI, go figure. So if you are even considering a future trial, it would be worthwhile now to see how you stack up for those qualifiers.
There are a slew of signaling pathways and a slew of them are being studied; but there is mounting evidence that Braf+ can yield some sensitivity to MEK pathways as well. The problem with pathways is they all have built in redudancies; that is to say though one pathway signal can be blocked, as is the case with V600, each pathway has built in mechanisms to re- route to another pathway, which is why Zelboraf has short term success. Here is another video link from the same conference that discusses signaling pathways http://www.youtube.com/watch?v=BhUXRmLdlvM&feature=relmfu
It is also worthwhile to look at Jerry from Fauq recent post anti-CTLA-4 and Anti-PD-1 antibody
Because I am a fan of IL2,, I found it interesting that in a recent study about PD1 cells http://onlinelibrary.wiley.com/doi/10.1002/eji.201040959/abstract,, it was found that they actually produce IL2. If that is true, it might follow that IL2 could help if you later did get into a PDI trial. Only an opinion.
Lastly, here is a link for an interesting trial for liver mets at MDA that you might find interesting http://www.clinicaltrials.gov/ct2/show/NCT00833807?cond=%22Melanoma%22&rank=185
Probably waaaaaaaaaaaaay more information than you wanted and as always take what you want and leave the rest !
Cheers,
Charlie S
-
- January 2, 2012 at 8:04 pm
Hey there Boots.
About surgery and IL2, I'm including a video link of a talk my surgical onc gave about surgery and the role of IL-2 in the era of Yervoy and Zelboraf at a recent Aim at Melanoma Conference http://www.youtube.com/watch?v=gOUtIy6T4oM&feature=relmfu.. The audio is a bit weak, so crank up the speakers. So,basically yes, surgery is an option and IL2 is an option, although many trials require measurable disease, few if any rule you out for either surgery or prior IL2 use.
And here is a link to a pretty up-to-date listing of the anti-PD1 trials and the exclusions. http://www.m-icab.org/images/stories/M-ICAB_table_-_final_small.pdf, skip the first listed worthless link. In essence, two weeks out from surgery prior to receiving trial drug.
Of note, many of these PD1 trials exclude prior use of Yervoy, many want an HLA typing of HLA-A02/HLA-A-0201 and many want either/or/and Melan-A, HMB-45, NY-ESO-1 positive tumors, but there is trial that looks at Zelboraf following IPI, go figure. So if you are even considering a future trial, it would be worthwhile now to see how you stack up for those qualifiers.
There are a slew of signaling pathways and a slew of them are being studied; but there is mounting evidence that Braf+ can yield some sensitivity to MEK pathways as well. The problem with pathways is they all have built in redudancies; that is to say though one pathway signal can be blocked, as is the case with V600, each pathway has built in mechanisms to re- route to another pathway, which is why Zelboraf has short term success. Here is another video link from the same conference that discusses signaling pathways http://www.youtube.com/watch?v=BhUXRmLdlvM&feature=relmfu
It is also worthwhile to look at Jerry from Fauq recent post anti-CTLA-4 and Anti-PD-1 antibody
Because I am a fan of IL2,, I found it interesting that in a recent study about PD1 cells http://onlinelibrary.wiley.com/doi/10.1002/eji.201040959/abstract,, it was found that they actually produce IL2. If that is true, it might follow that IL2 could help if you later did get into a PDI trial. Only an opinion.
Lastly, here is a link for an interesting trial for liver mets at MDA that you might find interesting http://www.clinicaltrials.gov/ct2/show/NCT00833807?cond=%22Melanoma%22&rank=185
Probably waaaaaaaaaaaaay more information than you wanted and as always take what you want and leave the rest !
Cheers,
Charlie S
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